Megan Sykes, MD
- Professor of Microbiology and Immunology and Surgical Sciences (in Surgery)
- Michael J. Friedlander Professor of Medicine
- Director, Columbia Center for Translational Immunology
Megan Sykes’ research career, during which she has published >420 papers and book chapters, has focused on hematopoietic cell transplantation, organ allograft tolerance induction, xenotransplantation tolerance and Type 1 diabetes. Dr. Sykes has developed novel strategies for achieving graft-versus-tumor effects without graft-versus-host disease following hematopoietic cell transplantation (HCT). She developed an approach that has been evaluated in clinical trials of non-myeloablative haploidentical HCT whose safety and efficacy allowed trials of HCT for the induction of organ allograft tolerance, allowing intentional achievement of tolerance in humans for the first time. Dr. Sykes has dissected the tolerance mechanisms and pioneered minimal conditioning approaches for using HCT to achieve allograft and xenograft tolerance. Her work on xenogeneic thymic transplantation for tolerance induction has led, for the first time, to long-term kidney xenograft survival in non-human primates. More recently, she has extended the HCT approach to the problem of reversing autoimmunity while replacing destroyed islets of Langerhans in Type 1 diabetes. She has developed novel “humanized mouse” models that allow personalized analysis of human immune disorders and therapies. Dr. Sykes is a Past President of the International Xenotransplantation Association, served as Vice President of TTS, has repeatedly served on TTS Council and is a member of the Institute of Medicine of the National Academies and of the Association of American Physicians.
Dr. Sykes believes that a mechanistic understanding of manipulations used to achieve clinical goals is essential to the translation of these manipulations to the clinic. It is for this reason that she has consistently worked at the interface between basic science and clinical applications, and has been able to translate her research to new treatments for patients requiring bone marrow or organ transplants. In 2010, after 20 years at Massachusetts General Hospital and Harvard Medical School, Dr. Sykes moved to Columbia University to establish the Columbia Center for Translational Immunology (CCTI). The CCTI is a multidisciplinary research center whose scope includes transplantation (organ and bone marrow), autoimmune disease, tumor immunology, infectious immunity and basic immunology. Currently, the CCTI has a staff of >100 scientists and support staff, including 16 faculty members. Dr. Sykes' own laboratory program currently includes major projects in the area of xenograft tolerance induction in humanized mouse models; unique humanized mouse models for the analysis and treatment of autoimmune diseases, including Type 1 diabetes and rheumatoid arthritis (the “personalized immune” mouse); studies of lymphocyte turnover, chimerism and T cell trafficking in patients receiving intestinal and liver transplants; tracking of alloreactive T cells in human transplant recipients; and both pre-clinical and clinical studies of non-myeloablative hematopoietic cell transplantation for the induction of allograft tolerance.
Our research has developed ways to utilize bone marrow transplantation as immunotherapy to achieve graft-versus-tumor effects while avoiding the common complication of such transplants, graft-versus-host disease. Another major area has been to utilize bone marrow transplantation for the induction of transplantation tolerance, both to organs from the same species (allografts) and from other species (xenografts). Our laboratory has worked toward the development of clinically feasible, non-toxic methods of re-educating the T cell, B cell and NK cell components of the immune system to accept allografts and xenografts without requiring long-term immunosuppressive therapy. We pioneered xenogeneic thymic transplantation as an approach to tolerance induction. We have demonstrated that non-myeloablative induction of mixed chimerism reverses the autoimmunity of Type 1 diabetes. We have recently developed novel humanized mouse models allowing "personalized" analysis of immune disease pathogenesis and immunotherapy. Additionally, we have developed novel tools for the analysis of the human alloresponse and are using these tools to better understand organ transplant immunobiology and tolerance in patients.
Education & Training
- MD, 1982 medicine, University of Toronto
- Internship: 1983 Montreal General Hospital
- Residency: Toronto General Hospital
Centers / Institutes / Programs
- Herbert Irving Comprehensive Cancer Center
Laboratory Leader, Senior Staff Fellow, Immunology Branch, National Cancer Institute, 1989-1991
NIH, Bethesda, MD
Assistant Immunologist, Departments of Surgery and Medicine, 1990-1992
Massachusetts General Hospital, Boston, MA
Assistant Professor, Departments of Surgery and Medicine (Immunology), 1990-1993
Harvard Medical School, Boston, MA
Associate Professor, Departments of Surgery and Medicine (Immunology), 1993-1999
Harvard Medical School, Boston, MA
Director of Cellular Immunology Laboratory, Transplantation Biology, 1990-2010
Research Center, Massachusetts General Hospital, Boston, MA
Associate Immunologist, Departments of Surgery and Medicine, 1992-1994
Massachusetts General Hospital, Boston, MA
Head, Bone Marrow Transplantation Section, Transplantation Biology, 1994-2010
Research Center, Massachusetts General Hospital, Boston, MA
Immunologist, Departments of Surgery and Medicine, 1995-2014
Massachusetts General Hospital, Boston, MA
Member, End Stage Renal Disease Program, Renal Unit, 1999-2010
Massachusetts General Hospital, Boston, MA
Professor, Department of Surgery (Immunology), 1999-2010
Harvard Medical School, Boston, MA
Professor, Department of Medicine, 2000-2010
Harvard Medical School, Boston, MA
Harold and Ellen Danser Professor, Department of Surgery, 2004-2010
Harvard Medical School, Boston, MA
Associate Director, Transplantation Biology Research Center, 2004-2010
Massachusetts General Hospital, Boston, MA
Director, Columbia Center for Translational Immunology, 2010-
Columbia University College of Physicians and Surgeons
Director of Research, Transplant Initiative, 2010-
Columbia University Medical Center
Director, Bone Marrow Transplantation Research, 2010-
Division of Hematology/Oncology, Department of Medicine, Columbia University Medical Center
Member, Columbia Stem Cell Initiative, 2010-
Columbia University Medical Cetner
Member, Lymphoid Malignancy Program Committee, 2010-
Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center
Member, Naomi Berrie Diabetes Center, 2010-
Columbia University Medical Center
Michael J. Friedlander Professor of Medicine and Surgery, 2010 -
Columbia University, New York, NY
Professor of Medicine, 2010 -
Columbia University, New York, NY
Professor of Microbiology and Immunology, 2010 -
Columbia University, New York, NY
Professor of Surgical Sciences, Surgery Department, 2010 -
Columbia University, New York, NY
Sykes M, Wolf S; Massachusetts General Hospital, Genetics Institute assignee. Use of IL-12 to prevent graft-vs-host disease. US Patent 5,573,764, 1996.
Sykes M, Sachs DH; Massachusetts General Hospital assignee. Xenograft Thymus. US Patent 5,658,564, 1997.
Sykes M, Sachs DH, Blancho G, LeGuern C; Massachusetts General Hospital assignee. Interleukin-10 and Immunosuppression. US Patent 5,624, 823, 1997.
Sykes M, Sachs DH; Massachusetts General Hospital assignee. Xenograft thymus. US Patent 08/243,652, 1997.
Sykes M; Massachusetts General Hospital assignee. Mixed chimerism and tolerance. US Patent 6,006, 752, 1999.
Sykes M; Massachusetts General Hospital assignee. Induced tolerance to xenografts. US Patent 6,296,486, 2001.
Sykes M, Sayegh M; The General Hospital Corporation assignee. Costimulatory blockade and mixed chimerism in allotransplantation. US Patent 6,280,957, 2001.
Sykes M; The General Hospital Corporation assignee. Mixed Chimerism and Tolerance. US Patent 6,412,492, 2002.
Sykes M; The General Hospital Corporation assignee. Costimulatory Blockade and Mixed Chimerism in Allo-Transplantation. US Patent 6,514,513, 2003.
Sykes M, Spitzer TR; The General Hospital Corporation assignee. Treatment of Hematologic Disorders. US Patent 6,558,662 B2, 2003.
Sykes M; The General Hospital Corporation assignee. Mixed Chimerism and Tolerance. US Patent 6,718,986, 2004.
Sykes M, The General Hospital Corporation assignee. Methods for Human Allografting. US Patent 7,332,157 B2, 2008.
Sykes M, Spitzer TR; The General Hospital Corporation assigness. Kits for Treatment of Hematologic Disorders. US Patent 7,408,039 B2, 2008.
Sykes M; The General Hospital Corporation assignee. Blockade of T Cell Migration into Epithelial GVHD Target Tissues as an Approach to Achieving Anti-Tumor Effects Against Lymphohematopoietic Malignancies without GVHD. US Patent 7,498,023, 2009
Sykes, M; The General Hospital Corporation assignee. Methods for Human Allografting. US Patent, 7,939,062, 2011
Sykes, M; The Trustees of Columbia University in the City of New York assignee. Genetic Modification of Pigs for Physiologic Hematopoietic Function in both Porcine and Human Environments. US Provisional Patent, 61/137,544, 2015
Member (with graduate student mentoring privileges), Committee on Immunology, Division of Medical Sciences, 1991-2010
Harvard Medical School, Boston, MA
Member, Harvard/Dana Farber Cancer Center, 2001-2010
Dana Farber Cancer Center, Boston, MA
Faculty Member, Harvard Program in Human Biology and Translational Medicine in the Programs in Biological and Biomedical Sciences Program, 2007-2010
Harvard Medical School, Boston, MA
Medical Student Immunology Course-Lecture on Transplantation Immunology, 2010-
One hour each year
Graduate Immunology Course, 2010-2013
Two one and a half hour classes per year
Member, Dept. of Microbiology & Immunology, Qualification Exam Committee, 2011
MD, PhD Program Research Seminar Series, One hour each year
Research Seminar Series- 1st year medical students, 2013-
One hour each year
Qualification Exam Committee, 2013-2014
Department of Microbiology & Immunology
Advisory and Supervisory Responsibilities
Graduate Student Sponsor
2-4 undergraduate, graduate and medical students in laboratory/year
Postdoctoral Fellow Advisor
8-10 postdoctoral fellows in laboratory/year
Committees / Societies / Memberships
American College of Physicians, Associate, 1985-1988
College of Physicians and Surgeons of Ontario, Member, 1985-
American Association of Immunologists, Member, 1989-
The Transplantation Society, Member, 1990-
International Society for Experimental Hematology, Member, 1991-
American Society of Hematology, Member, 1992-
American Society for Blood and Marrow Transplantation, Member, 1994-
American Society of Transplantation, Member, 1996-
Councilor, International Xenotransplantation Association, 1998-2001
American Diabetes Association, Member, 1999-
Councilor, The Transplantation Society, 2000-2006
Councilor, International Xenotransplantation Association, 2001-2005
President, International Xenotransplantation Association, 2005-2007
Vice President, The Transplantation Society, 2006-2010
Councilor, Interurban Clinical Club, 2007-2010
Councilor, The Transplantation Society, 2013-2016
New York Academy of Science, Member, 2014-2015
National Institute of Allergy and Infectious Diseases Advisory Council, 2005-2009
AAI Nominating Committee, 2005-2006
NHLBI Strategic Planning (Cellular Therapeutics), 2006
AAI Block Co-Chair, Transplantation Immunology, 2006
Advisory Board of the Lawrence Transplant Foundation, 2006
The Transplantation Society Communications Committee, 2006-
Representative for The Transplantation Society to Federation of Clinical Immunology Societies Steering Committee, 2006-2008
Member, Xenotransplant Program Subcommittee for the 2008 Congress of the Transplantation Society, 2006-2008
Member, International Advisory Committee for the 2008 Congress of the Transplantation Society, 2006-2008
The Transplantation Society Ethics Committee, 2006-2010
NIAID T32, Interdisciplinary Training in Transplantation Biology, University of Pittsburgh, Scientific Advisory Board, 2007-
Member, Scientific and Medical Research Funding Working Group, California Institute for Regenerative Medicine, 2008-
Member, Ad hoc Planning and Evaluation Panel for Clinical Research Efforts Supported by the Special Funding Program for Type 1 Diabetes, NIDDK, 2008
Member, Advisory Board, Faculty of 1000 Biology, 2008-2010
Participant, First Global Consultation on Regulatory Requirements for Xenotransplantation, 2008
Clinical Trials, World Health Organization, Changsha, China, November 17-22, 2008
Leader, Task Force on Basic Science, The Transplantation Society, 2008-
FOCIS Nominating Committee, 2010
Ad Hoc Member, Cancer Immunopathology and Immunotherapy Study Section, NIH, 2010
Member, Scientific Council, Institut Hospitalo Universitaire, 2010
Member, Blood and Marrow Transplant Clinical Trials Network Review Panel, NIH, 2011
Member, Expert Panel for the Special Statutory Funding Program for Type 1 Diabetes Research, NIDDK, 2011
Ad Hoc Member, Board of Scientific Counselors, National Heart, Lung, and Blood Institute, NIH 2011
Member, Scientific Advisory Board, Diabetes Research Institute, University of Miami Miller School of Medicine, 2011
Member, Steering Committee, Women in Transplantation Program, The Transplantation Society, 2011-
Women in Transplantation (WIT) Mentor (Nina Pilat-Michalek and Evelyn Salvaris), 2011-
Ad Hoc Member, Cancer Immunopathology and Immunotherapy Study Section, NIH, 2012
Member, Communications Committee, The Transplantation Society, 2012
Member, Special Emphasis Panel on Transplantation, Tolerance & Tumor Immunology, NIH, 2012
Chair, Research Using Subjects from TrialNet Living Biobank Review Panel, NIDDK, NIH, 2012
Member, DMICC Workshop on Research Supported by the Special Statutory Funding Program for Type 1 Diabetes Research, NIDDK, NIH, 2013
Ad Hoc Reviewer, Mentor-Based Postdoctoral Fellowship Awards, American Diabetes Association, 2013
At-Large Director, Board of Directors, Federation of Clinical Immunology Societies, 2013-
Member, Transplantation, Tolerance, and Tumor Immunology Study Section, Center for Scientific Review, NIH, 2013-2017
Co-Chair, Abstract Review Committee, World Transplant Congress Meeting, 2013-2014
Chair, Keynote Symposium, International Xenotransplantation Association Congress, Osaka, Japan, 2013
Ad Hoc Reviewer, Mentor-Based Postdoctoral Fellowship Awards, Roche Organ Transplantation Research Foundation (ROTRF), 2013
Member, Lupus Drug Repurposing Vetting Committee Meeting, Boston, MA, 2014
Ad Hoc Reviewer, Cancer Immunopathology and Immunotherapy Study Section (CII), NIH, 2014
Basic Science Co-Chair, Scientific Program Committee, 2016 International Congress of the Transplantation Society, 2014-2016
Selection Committee, Woman Leader in Transplantation Award, 2014
Chair, Institute of Medicine Interest Group 13 on Cancer, Stem Cell Biology and Transplantation, 2014-2016
Co-Chair, Journal Committee, 2016 International Congress of the Transplantation Society, 2014-
Expert Reviewer, Transplant Library (Centre for Evidence in Transplantation), 2014-
Award Selection Committee Member, Basic/Translational Science Award, The Transplantation Society, 2014
Abstract Reviewer, FOCIS 2015, 2014-
Children’s Cancer Research Institute, Vienna, Scientific Advisory Board member, 2014-
Co-Chair, Symposium 3, 37th Annual Meeting of the Japan Society for Hematopoietic Cell Transplantation, 2015
Co-Chair, Thematic Symposium, The Best of Transplantation, 2015, FOCIS, San Diego, 2015
Chair, Symposium: Immunosuppression & Tolerance, IPITA IXA CTS Joint Congress, Melbourne, Australia, 2015
Co-Chair, Abstract Driven Session: Tolerance & Zoonosis, IPITA IXA CTS Joint Congress, Melbourne, Australia, 2015
Labex IGO, Scientific Advisory Board, Nantes, France, 2014-
Chair of Session Immunologic Crossroads in Transplantation Tolerance: An Optimal and Feasible Solution, FOCIS Boston, MA, 2016
Scientific Advisory Board, NIH/NIAID Systems Biology of Antibacterial Resistance grant, UCLA, 2016
Chair of Post-Graduate Course on Computational Immunology, TTS Conference, Hong Kong, China, 2016
Plenary Chair: Basic and Translational Sciences, TTS Conference, Hong Kong, China, 2016
Starr Cancer Consortium: Scientific Advisory Board, New York, NY, 2014-
FOCIS Nominating Committee, Boston, MA, 2016-
Consultant, New Leaf Venture Partners, 2016
Consultant, Magenta Therapeutics, 2016
Congress Board Member, 2017 International Xenotransplantation Association Congress, Maryland, 2017
Consultant, Recombinetics, 2017
Chair, Human Immunity to Islets, HIRN 2017 Annual Investigator Meeting, 2017
Consultant, Flagship Pioneering, 2017
Consultant, Bayer Healthcare, 2017
Consultant, Ossium Health Corporation, 2017
Consultant, Editas Medicine, 2017
FOCIS 2017 Session Chair, Thematic Symposia, Alarmins as Immune Targets, 2017
Session Chair Oral Abstract Sessions, The Forefront of Immune Regulation
Member, Scientific Program Committee, 2018 International Congress of The Transplantation Society, 2018
Honors & Awards
1991 American Cancer Society Junior Faculty Research Award
1998 Wyeth-Ayerst Young Investigator Award, American Society of Transplant Physicians
1999 Honorary Master of Arts Degree, Harvard Medical School
2002 Moses Baron Lecture, University of Minnesota, MN
2005 Elected to membership, Interurban Clinical Club
2007 American Society of Transplantation (AST) Basic Science Established Investigator Award
2007 Honorary Professorship, Wenzhou Medical College
2009 Distinguished Lecturer, American Association of Immunologists Annual Meeting
2009 Fellow, AAAS (American Association for the Advancement of Science)
2009 Martin Research Prize for Excellence in Clinical Research, MGH
2009 Erwin Neter Memorial Lecture, Association of Medical Laboratory Immunologists
2009 8th Annual Catherine Tuck, MD Memorial Lecture
2009 Elected to membership, Institute of Medicine of the National Academies
2010 Elected to membership, Association of American Physicians
2010 TTS Roche Award for Outstanding Achievement in Transplantation Science (Basic)
2012 Pixie Campbell Memorial Lecture, 13th Annual Colorado Immunology Conference
2014 Award for Outstanding Achievement in Transplantation (Basic Science), The Transplantation Society
2015 Dean’s Distinguished Lecture in the Clinical Sciences, Dean’s Distinguished Lecture Series of the College of Physicians and Surgeons, Columbia University Medical Center
2016 Elected to membership The Practitioners Society, New York
2017 Elected to Honorary Membership, International Xenotransplantation Association
- Graft-versus-host disease
- Transplantation tolerance
- Type 1 diabetes autoimmunity
American Cancer Society, Principal Investigator, 1991
Achieving the Graft-vs-Leukemia Effect Without GVHD (declined)
NIH/NCI, Principal Investigator, Achieving the Graft-vs-Leukemia Effect Without GVHD, 1991-1994
NIAID, Principal Investigator, A New Approach to Preventing GVHD, 1991-1995
NIH/NCI, R01, Co-Investigator, IL-2 in HLA Mismatched Bone Marrow Transplantation, 1994-1996
NHLBI, Co-Investigator, Retroviral Transduction of a Class I MHC Gene, 1993-1997
NIH/NCI, R01, Principal Investigator, T Cell Activities Promoting GVL, GVHD and Alloengraftment, 1994-1998
American Cancer Society, Principal Investigator, Achieving Graft-vs-Leukemia Effects without Graft-vs-Host Disease, 1995-1998
Sponsored Research Agreement, BioTransplant, Inc., Co-Investigator, Xenograft Research in Miniature Swine, 1991-1999
Sponsored Research Agreement, Bio Transplant, Inc., Role of Chemokines in GVHD Pathogenesis, 2001-2002
Sponsored Research Agreement, Bio Transplant, Inc., Avoiding Irradiation in Mixed Chimeras, 2001-2002
Sponsored Research Agreement, Bio Transplant, Inc., Pig Cytokines for Enhancement of Chimerism and Tolerance in a Mouse Model, 2001-2002
NIH/NHLBI, P01, Project Leader, Component Project 4: Xenogeneic Tolerance in Mice, 1998-2003
Tolerance: An Approach to Cardiac Allo- and Xenotransplants
Juvenile Diabetes Foundation, Principal Investigator, Project #10: Mixed Bone Marrow, 1998-2003
Chimerism as a Treatment for Diabetes, JDF Center for Islet Transplantation at HMS
NIH/NIAID, R01, Principal Investigator, T and B Cell Tolerance in Human Mixed Chimeras, 1999-2003
NIH/NCI, R01, Co-Investigator, Mixed Chimerism Following BMT for Hematologic Malignancy, 2000-2003
NIH/NHLBI, R01, Principal Investigator, Compatibility of Swine Stem Cells and Human Stroma, 1996-2004
NIH/NCDDG-HIV, P01, Principal Investigator (Program Director), Program Project Grant, 1996-2005
Xenogeneic Stem Cell and Thymic Replacement in AIDS
NIAID/NIDDK/JDRF Immune Tolerance Network, Subcontract Principal Investigator, 2001-2006
Combined HLA-Matched Bone Marrow and Kidney Transplantation for Multiple Myeloma With Renal Failure
NIAID Bioinformatics Integration Support Contract (BISC) System Scientific Advisory Board, 2003-2007
Multiple Myeloma Research Foundation: Immunobiology of Donor Lymphocyte infusions (DLI), 2004-2005
to separate GVHD and GVT effects
Multiple Myeloma Research Foundation; Principal Investigator, Immunobiology of Lymphohematopoietic GVH Reactions, 2006-2007
Lymphohematopoietic GVH Reactions.
JDRF, Program Project Grant, JDRF Center on Immunological Tolerance in Type 1 Diabetes. 2003-2007
Project Leader, Project #5: Mixed Chimerism in Diabetic NOD Mice
NIH/NIAID R01 Principal Investigator, T and B Cell Tolerance via Marrow Transplantation, 2003-2008
(declined because project was funded under PO1 # HL18646-26)
NIH/NHLBI, P01 Tolerance: An approach to Cardiac Allo and Xenotransplantation, 2003-2008
Project Leader, Project #3 T & B cell tolerance in presensitized mice
NIH/NCI, R01, Principal Investigator, Separation of GVH and GVL in Mouse Models,1999-2009
Multiple Myeloma Research Foundation, Senior Research Award, Stem Cell Rejection to Induce Anti-tumor Immunity, 2007-2009
NIH/NIAID, P01, Thymic Xenotransplantation for Immune Restoration, 2005-2010
Project Leader, Project 3: Porcine Thymic Transplantation to Mice with Human Immune Systems
JDRF, Basic Science Grant, Principal Investigator, Tolerance Induction by Xenogeneic Thymic Transplantation, 2007-2010
NIH/NIAID, R21, Principal Investigator, In Vivo Delivery of siRNAs as a Novel Approach to Inducing Mixed Chimerism, 2009-2011
NIH/NHLBI, R01, Principal Investigator, Mixed Chimerism as an Approach to Transplant Tolerance, 1993-2011
NIH/NCI, P01, Principal Investigator (Program Director) GVL without GVHD across HLA Barriers: Translational Studies. 2006-2011
NIH/NCI, R01, Principal Investigator, Control of CD4 and CD8-mediated GVHR, 2006-2011
(declined because project was funded under PO1#CA 111519-01A2)
ROTRF, Principal Investigator, Achieving durable mixed chimerism using regulatory cells in non-human primates, 2001-2012
JDRF, Program Project Grant, JDRF Center on Immunological Tolerance in Type 1 Diabetes, 2008-2012
Project Leader, Project #3: Regulation and homeostasis of diabetic human T cells
NIH/Immune Tolerance Network, Co-Principal Investigator, Renal Allograft Tolerance through Mixed Chimerism, 2008-2014
NIH/NIAID, R01, Principal Investigator, Mechanisms of tolerance in recipients of combined kidney and, 2009-2012
bone marrow transplants
NIH/NHLBI/ARRA, Co-Investigator, Immune response to allogeneic hESC-derived endothelial cells in hu-mice. 2010-2012
NIH/NIAID R01, Principal Investigator, Antibody Tolerance by Mixed Chimerism Induction, 2009-2014
(declined because project was funded under PO1#HL18646)
Helmsley Foundation, Co-Investigator, Generation of Thymic Epithelial Cells from Human Pluripotent Stem Cells, 2014-2015
Frederick Banting Foundation, Principal Investigator, Durable Mixed Chimerism for Islet Allograft Tolerance, 2013-2015
ROTRF, Principal Investigator, A blood biomarker of kidney transplant outcomes: tracking and donor-reactive T cells, 2014-2015
NIH/NIDDK, R01, Co-Investigator, Contribution of B cells to Human Cardiac Allograft Vasculopathy, 2015-2016
NIH/ITN, Principal Investigator, Tracking T regulatory cells in ITN036 CKBMT patients, 2014-2016
NIH/NAIMS, R21, Co-Investigator, An RA immune system derived from patient’s stem cells, 2013-2016
NIH/NIAID, R01, Principal Investigator, Pig to human thymic xenotransplantation, 2010-2016
NIH/NIAMS P30, Co-Investigator, Columbia University Medical Center Skin Disease, 2010-2016
Research Center; Flow Cytometry Core
NIH/NIDDK, P30, Core Leader, Diabetes & Endocrinology Research Center, Flow Cytometry Core, 2014-2018
NIH/NIAID, P01, Principal Investigator (Contact PI), A Tolerance Approach to Xenotransplantation; 2001-2017
Proj 3: Tolerance of Adaptive and Innate Human Anti-Pig Immune Responses in Humanized Mice
NIH/NIAID, P01, Project Leader, Tissue compartmentalization of human lymphocytes; 2013-2018
Proj 4: Lymphocyte reconstitution and responses in intestinal transplantation
NIH/NHLBI, P01, Co-Investigator, New Approaches to Cardiothoracic Tolerance Induction, 2009-2019
NIH/NIDDK, UC4, Principal Investigator, Mice with Autologous Human T1d-derived Immune, 2014-2019
Systems and iPSC-derived Beta Cells
Stemnion, Principal Investigator, Facilitating mixed allogeneic chimerism induction by, 2015-2017
co-transplantation of Amnion-derived Multipotent Progenitor Cells (AMP cells) in humanized mice with established immune system
DoD, CDMRP, Principal Investigator, Reconstructive Transplantation Research Award, 2015-2017
Establishment of Donor Chimerism Using Allogeneic Bone Marrow with AMP Cell Co-Infusion
NIH/OD R01, Principal Investigator, Robust allograft tolerance in non-human primates, 2015-2020
NIH/NIDDK, R01, Principal Investigator, Immune Response to iPSC-derived Beta Cells in Type 1 Diabetes, 2015-2019
United Therapeutics/Lung Biotechnology, Principal Investigator, Collaboration on Xenograft lung Tolerance, 2015-2018
NIH/NIAID, R56, Principal Investigator, Immune response to combined liver and bone marrow, 2016-2017
transplant for tolerance in NHP
CELLDEX Therapeutics, Principal Investigator, Combined use of FLt3L and rapamycin to promote, 2016-2018
durable mixed allogeneic chimerism in NHP
NIH/NIAID, U01, Co-Investigator Effects of inhibiting early inflammation in kidney transplant patients, 2016-2017
NIH/NIAID, R56, Co-Investigator, Tolerance to Vascularized Allografts in Miniswine, 2017-2018
JDRF, SRA, Co Investigator, Improving engraftment and survival of pig islet xenografts, 2017
through transgenic expression of human CD47
ITB-MED, Sponsored Research Project, Principal Investigator, Effect of Siplizumab, 2017
on natural Tregs and effector T cells
NIH-NIAID, U19, Principal Investigator, Regulatory T cells to promote mixed chimerism for, 2017-2022
tolerance to islets and kidneys from deceased and living donors
NIH/NIAID, PO1, Contact Principal Investigator, Project Leader, Tolerance of Adaptive and Innate, 2017-2021
Human Anti-Pig Immune Responses in Humanized Mice
NIH/NIAID, RO1, Principal Investigator, Immune response to combined, 2017-2022
liver and bone marrow transplantation for tolerance in NHP
NIH/NIAID, RO1, Principal Investigator, Tolerance of Adaptive and Innate Human Anti-pig, 2017-2022
Immune Responses in Humanized Mice
NIH/NIDDK, UC4, Contact Principal Investigator, A pipeline for analysis of diabetogenic T cell receptors In vivo, 2017-2021
NIH/NIAID, R34, Multiple Principal Investigator, Study of Intestinal Transplantation with Emphasis on Rejection, 2017-2018
NIH/NCATS, R21, Principal Investigator, TCR and BCR deep sequencing to distinguish, 2017-2019
autoimmune recurrence from allograft rejection
TISSUE COMPARTMENTALIZATION OF HUMAN LYMPHOCYTES (Federal Gov)
Jun 25 2018 - May 31 2023
INTESTINAL ALLOGRAFT TOLERANCE IN LARGE ANIMALS (Federal Gov)
Feb 8 2018 - Jan 31 2023
REGULATORY T CELLS TO PROMOTE MIXED CHIMERISM FOR TOLERANCE TO ISLETS ANDKIDNEYS FROM DECEASED AND LIVING DONORS (Federal Gov)
Aug 18 2017 - Jul 31 2022
A TOLERANCE APPROACH TO XENOTRANSPLANTATION (Federal Gov)
Aug 1 2017 - Jul 31 2021
A PIPELINE FOR ANALYSIS OF DIABETOGENIC T CELL RECEPTORS IN VIVO (Private)
Jan 1 2018 - Dec 31 2020
A SPECIFIC BIOMARKER FOR THE HOST ANTI-DONOR T CELL RESPONSE (Private)
Oct 1 2018 - Sep 30 2020
TCR AND BCR DEEP SEQUENCING TO DISTINGUISH AUTOIMMUNE RECURRENCE FROM ALLOGRAFT REJECTION (Federal Gov)
Aug 1 2018 - Jul 31 2020
ROBUST ALLOGRAFT TOLERANCE IN NON-HUMAN PRIMATES (Federal Gov)
Jul 1 2015 - Mar 31 2020
IMMUNE RESPONSE TO IPSC-DERIVED BETA CELLS IN TYPE 1 DIABETES (Federal Gov)
Apr 1 2015 - Mar 31 2020
CONTRIBUTION OF B CELLS TO HUMAN CARDIAC ALLOGRAFT VASCULOPATHY (Federal Gov)
Aug 1 2015 - Jan 31 2020
MICE WITH AUTOLOGOUS HUMAN T1D-DERIVED IMMUNE SYSTEMS AND IPSC-DERIVED BETA CELL (Federal Gov)
Sep 25 2014 - Jun 30 2019
DIABETES AND ENDOCRINOLOGY RESEARCH CENTER (Federal Gov)
Mar 15 2013 - Jan 31 2019
EFFECTS OF INHIBITING EARLY INFLAMMATION IN KIDNEY TRANSPLANT PATIENTS (Federal Gov)
Sep 1 2016 - Aug 31 2018
A TOLERANCE APPROACH TO XENOTRANSPLANTATION (Private)
Aug 6 2015 - Aug 5 2018
ISLET-REACTIVE TCR CLONES IN HUMANIZED MICE GENERATED WITH TYPE 1 DIABETES PATIENT VS. HEALTHY CONTROL HEMATOPOIETIC STEM CELLS (Federal Gov)
Jul 1 2017 - Jun 30 2018
IMPROVING ENGRAFTMENT AND SURVIVAL OF PIG ISLET XENOGRAFTS THROUGH TRANSGENIC EXPRESSION OF HUMAN CD47 (Private)
Mar 1 2017 - Feb 28 2018
TOLERANCE TO VASCULARIZED ALLOGRAFTS IN MINISWINE (Federal Gov)
Apr 1 1991 - Jan 31 2018
COMBINED USE OF FLT3L AND RAPAMYCIN TO PROMOTE DURABLE MIXED ALLOGENEIC CHIMERISM IN A HUMANIZED MOUSE MODEL (Private)
Feb 18 2016 - Jan 17 2018
FACILITATING NIXED ALLOGENEIC CHIMERISM INDUCTION BY CO-TRANSPLANTATION OF ANMION-DERIVED MUTIPOTENT PROGENITOR CELLS (AMP CELLS) IN HUMANIZED MICE WITH ESTABLISHED IMMUNE SYSTEM (Private)
Jan 20 2015 - Dec 31 2017
FACILITATING MIXED ALLOGENEIC CHIMERISM INDUCTION BY COTRANSPLANTATION OF AMNION-DERIVED MULTIPOTENT PROGENITOR CELLS (AMP CELLS) IN HUMANIZED MICE WITH ESTABLISHED IMMUNE SYSTEM (Private)
Sep 7 2016 - Sep 6 2017
ESTABLISHMENT OF DONOR CHIMERISM USING ALLOGENEIC BONE MARROW WITH AMP CELL CO-INFUSION (Federal Gov)
Aug 15 2015 - Aug 14 2017
IMMUNE RESPONSE TO COMBINED LIVER AND BONE MARROW TRANSPLANT OR TOLERANCE IN NHP (Federal Gov)
Aug 19 2016 - Jul 31 2017
COLUMBIA UNIVERSITY MEDICAL CENTER SKIN DISEASE RESEARCH CENTER (CUMCSDRC) (Federal Gov)
Jul 20 1997 - Jun 30 2017
NEXT GENERATION OF RESEARCH SCIENTISTS AWARD (Private)
Jun 1 2016 - May 31 2017
A TOLERANCE APPROACH TO XENOTRANSPLANTATION (Federal Gov)
Jul 15 2011 - Jun 30 2016
PIG TO HUMAN THYMIC XENOTRANSPLANTATION (Federal Gov)
May 1 2010 - Apr 30 2016
AN RA IMMUNE SYSTEM DERIVED FROM PATIENT S STEM CELLS (Federal Gov)
Jul 1 2013 - Mar 31 2016
NEW APPROACHES TO CARDIOTHORACIC TOLERANCE INDUCTION (Federal Gov)
Nov 14 2014 - Oct 31 2015
A BLOOD BIOMARKER OF KIDNEY TRANSPLANT OUTCOMES: TRACKING AND DONOR-REACTIVE T CELLS (Private)
Nov 1 2014 - Oct 31 2015
CELL INTRINSIC IMMUNOPATHOLOGY OF TYPE 1 DIABETES IN HUMANIZED MICE (Federal Gov)
Jul 1 2012 - Jun 30 2015
CELL INTRINISC IMMUNOPATHOLOGY OF TYPE 1 DIABETES IN HUMANIZED MICE (Private)
Jul 1 2011 - Jun 30 2015
IMMUNE TOLERANCE NETWORK (Federal Gov)
May 1 2014 - Jan 31 2015
DURABLE MIXED CHIMERISM FOR ISLET ALLOGRAFT TOLERANCE (Private)
Sep 1 2013 - Aug 31 2014
MECHANISM OF T CELL TOLERANCE IN PATIENTS RECEIVING COMBINED KIDNEY AND BONE MARROW TRANSPLANTATION (Private)
Jul 1 2013 - Jun 30 2014
COLLABORATIVE EFFORT IN STEM CELL BIOLOGY (Private)
Jul 1 2010 - Jun 30 2014
INTENTIONAL REJECTION OF THE DONOR GRAFT USING RLI... (Private)
Jun 1 2013 - May 31 2014
ANTIBODY TOLERANCE BY MIXED CHIMERISM INDUCTION (Federal Gov)
May 14 2010 - Apr 30 2014
DEVELOPMENT OF SPECIFIC TOLERANCE IN PIG-TO-HUMAN THYMIC TRANSPLANTATION MODEL USING HUMANIZED MICE (Private)
Jul 1 2011 - Jun 30 2013
THE COLLABORATIVE NETWORK FOR CLINICAL RESEARCH IN IMMUNE TOLERANCE (Federal Gov)
Jan 1 2011 - Apr 30 2013
ACHIEVING DURABLE MIXED CHIMERISM USING REGULATORY CELLS IN NON-HUMAN PRIMATES (Private)
Jan 1 2011 - Dec 31 2012
REGULATION AND HOMEOSTASIS OF DIABETIC HUMAN (Private)
Apr 1 2010 - Dec 31 2012
MECHANISMS OF TOLERANCE IN RECIPIENTS OF COMBINED KIDNEY AND BONE MARROW TRANSPLANT (Federal Gov)
Aug 11 2009 - Jul 31 2012
GVL WITHOUT GVHD ACROSS HLA BARRIERS: TRANSLATIONAL STUDIES (Federal Gov)
Sep 12 2006 - Jul 31 2012
REGULATORY T CELLS FOR PROMOTION OF DURABLE MIXED HEMATOPOIE TIC CHIMERISM AND IMMUNE TOLERANCE IN A NONHUMAN PRIMATE MOD (Private)
Jul 1 2011 - Jun 30 2012
STUDY OF THE IMMUNOLOGICAL MECHANISMS INVOLVED IN TRANSPLANA TION TOLERANCE AFTER COMBINED KIDNEY: BONE MARROW TRANSPLANT (Private)
Jul 1 2010 - Jun 30 2012
SUPPLY FUNDS FOR GODA (Private)
May 9 2011 - May 8 2012
IMMUNE RESPONSE TO ALLOGENEIC HESC-DERIVES ENDOTHELIAL CELLS (Federal Gov)
Apr 21 2010 - Mar 31 2012
MIXED CHIMERISM APPROACH TO TRANSPLANTATION TOLERANCE (Federal Gov)
Jun 1 1994 - Feb 28 2012
TRAINING IN TRANSPLANTATION BIOLOGY (Federal Gov)
Sep 1 2010 - Aug 31 2011
INFLUENCE OF AUTOIMMUNITY ON ISLET XENOGRAFT SURVIVAL IN NOD MICE (Private)
Sep 1 2010 - Mar 1 2011
- Hao Wei Li, PhD, Faculty Researcher
- Sean Campbell, MD, PhD, Postdoctoral Researcher
- Shana Coley, MD, Postdoctoral Researcher
- Nicole Danzl, PhD, Postdoctoral Researcher
- Jianing Fu, PhD, Postdoctoral Researcher
- Mohsen Khosravi Maharlooei, MD, Postdoctoral Researcher
- Elias Spyrou, MD, PhD, Postdoctoral Researcher
- Elizabeth Waffarn, PhD, Postdoctoral Researcher
- Rachel Madley, Student
- Grace Nauman, Student
- Xiaolan Ding, Lab Technician
- Brittany Shonts, Lab Technician
427. Borsotti C, Danzl NM, Nauman G, Hölzl MA, French C, Chavez E, Khosravi-Mararlooei M, Glauzy S, Delmotte FR, Meffre E, Savage DG, Campbell SR, Goland R, Greenberg E, Bi J, Satwani P, Yang S, Bathon J, Winchester R, Sykes M. HSC-extrinsic sex- and intrinsic autoimmune disease-related human B cell variation is recapitulated in humanized mice. Blood Advances. 2017. In Press.
426. Kato Y, Griesemer AD, Wu A, Sondermeijer HP, Weiner JI, Duran-Struuck R, Martinez M, Slate AR, Romanov A, Lefkowitch JH, Sykes M, Kato T. Novel H-shunt Venovenous Bypass for Liver Transplantation in Cynomolgus Macaques. Comp. Med. 2017 Oct. In Press.
425. Tan S, Li Y, Xia J, Jin CH, Hu Z, Duinkerken G, Li Y, Khosravi Maharlooei M, Chavez E, Nauman G, Danzl N, Nakayama M, Roep BO, Sykes M, Yang YG. Type 1 diabetes induction in humanized mice. Proc Natl Acad Sci. 2017 Sep 5. pii: 201710415. doi: 10.1073/pnas.1710415114. [Epub ahead of print] PMID: 28874533
424. Yamada K, Sykes M, Sachs D. Tolerance in xenotransplantation. Curr Opin Organ Tran. 2017. In Press
423. Tan, S., Xia, J., Hu, Z., Li, Y., Duinkerken, G., Jin, CH., Li, Y., Danzl, N., Nakayama, M., Roep, B., Sykes, M., Yang, YY. Human CD4 cells engineered to express a patient-derived islet autoreactive T-cell receptor cause type 1 diabetes in humanized mice. Proc Nat Acad Sci. 2017. In Press.
422. Sui L, Chen X, Leibel R, Sykes M, Egli D. Beta cell replacement in mice using human type 1 diabetes nuclear transfer embryonic stem cells. Diabetes. 2017. In Press
421. Zuber J, Sykes M. Mechanisms of Mixed Chimerism-Based Transplant Tolerance. Trends Immunol. 2017 Aug 18. pii: S1471-4906(17)30146-1. doi: 10.1016/j.it.2017.07.008. [Epub ahead of print] PMID: 28826941
420. DeWolf S, Sykes M. Alloimmune T cells in transplantation. J Clin Invest. 2017 Jun 30;127(7):2473-2481. doi: 10.1172/JCI90595. Epub 2017 Jun 19. PMCID: PMC5490749
419. Gao B, Gu Y, Rong C, Moore C, Porcheray F, Wong W, Preffer FI, Saidman SL, Fu Y, AB Cosimi B, Sachs DH, Kawai T, Sykes M, Zorn E. Dynamics of B cell recovery following kidney/bone marrow transplant recipients. Transplantation. 2017 Apr 19. doi: 10.1097/ TP.0000000000001789. [Epub ahead of print] PMID: 28422925
418. Sprangers B, DeWolf S, Savage TM, Morokata T, Obradovic A1, LoCascio SA, Shonts B1, Zuber J, Lau SP, Shah R, Morris H, Steshenko V, Zorn E, Preffer FI, Olek S, Dombkowski DM, Turka LA, Colvin R, Winchester R, Kawai T, Sykes M. Origin of enriched regulatory t cells in patients receiving combined kidney/bone marrow transplantation to induce transplantation tolerance. Am J Transplant. 2017 Mar 1. doi: 10.1111/ajt.14251. Epub 2017 Apr 10. PMID: 28251801
417. Weiner J, Zuber J, Shonts B, Yang S, Fu J, Martinez M, Farber D, Kato T, Sykes M. Long-term persistence of innate lymphoid cells in the gut after intestinal transplantation. Transplantation. 2016 Dec 8, DOI: 10.1097/TP.0000000000001593. [Epub ahead of print] PMCID: PMC4228952
416. Duran-Struuck R, Buhler L, Alonso-Guallart P, Zitsman J, Kato Y, Wu A, McMurchy A, Woodland D, Griesemer A, Martinez M, Boskovic S, Kawai T, Cosimi A, Wuu C, Slate A, Mapara M, Baker S, Tokarz R, D’Agati V, Hammer S, Pereira M, Lipkin W, Wekerle T, Levings M, Sykes M. Effect of ex vivo expanded recipient regulatory T cells on hematopoietic chimerism and kidney allograft tolerance across MHC barriers in cynomolgus macaques. Transplantation. 2017 Feb;101 (2):274-283, DOI: 10.1097/TP.0000000000001559. PMCID: PMC5263090
415. Zuber J, Shonts B, Lau S, Obradovic A, Fu J, Yang S, Lambert M, Coley S, Weiner J, Thome J, DeWolf J, Farber D, Shen Y, Caillat-Zucman S, Bhagat G, Griesemer A, Martinez M, Kato T, Sykes M. Bidirectional intragraft alloreactivity drives the repopulation of human intestinal allografts and correlates with clinical outcome. Science Immunology 07 Oct 2016: Vol. 1, Issue 4 eaah3732, DOI: 10.1126/sciimmunol.aah3732 PMCID: PMC5323244
414. Li HW, Vishwasrao P, Holzl MA, Chen S, Choi G, Zhao G, Sykes M. Impact of Mixed Xenogeneic Porcine Hematopoietic Chimerism on Human NK Cell Recognition in a Humanized Mouse Model. Am J Transplant. 2017 Feb;17 (2):353-364. doi: 10.1111/ajt.13957. Doi: 10.11111/ajt. Epub 2016 Aug 10.PMC5414033
413. Xia J, Hu Z, Yoshihara S, Li Y, Jin CH, Tan S, Li W, Chen Q, Sykes M, Yang YG. Modeling Human Leukemia Immunotherapy in humanized mice. EBiomedicine 2016 Jun 23 pii: S2352-3954 (16)30285-7 Doi: 10.1016/j.ebiom.2016.06.028. PMCID: PMC5006579
412. Bartlett ST, Markmann JF, Johnson P, Korgren O, Hering BJ, Scharp D, Kay TW, Bromberg J, Odorico JS, Weir GC, Bridges N, Kandaswamy R, Stock P, Friend P, Gotoh M, Cooper DK, Park CG, O;Connell P, Stabler C, Matsumoto S, Ludwig B, Choudhary P, Kovatchev B, Rickels MR, Sykes M, Wood K, Kraemer K, Hwa A, Stanley E, Ricordi C, Zimmerman M, Greenstein J, Montanya E, Otokoski T. Report from IPITA-TTS Opinion Leaders Meeting on the Future of β-Cell Replacement. Transplantation. 2016Jul 100(7):e25-31. Doi: 10.1097 PMCID: PMC4741413
410. Hirata Y, Li HW, Takahashi K, Ishii H, Sykes M, Fujisaki J. MHC Class I Expression by Donor Hematopoietic Stem Cells Is Required to Prevent NK Cell Attack in Allogeneic, but Not Syngeneic Recipient Mice. PLoS One. 2015 Nov 6; 10(11):e0141785. Doi: 10.1371/journal.pone.014785, eCollection 2015. PMCID: PMC4636372
409. Newell KA, Asare A, Sanz I, Wei C, Rosenberg A, Gao Z, Kanaparthi S, Asare S, Lim N, Stahly M, Howell M, Knechtle S, Kirk A, Marks WH, Kawai T, Spitzer T, Tolkoff-Rubin N, Sykes M, Sachs DH, Cosimi AB, Burlingham WJ, Phippard D, Turka LA. Longitudinal studies of a B cell-derived signature of tolerance in renal transplant recipients. American Journal of Transplantation. 2015 Nov; 15(11):2908-20. Doi: 10.1111/ajt.13480. Epub 2015 Oct 13. PMCID: PMC4725587
408. DeWolf S, Morris H, Shen Y, Sykes M. Author response to comment on "Tracking donor-reactive T cells: Evidence for clonal deletion in tolerant kidney transplant patients". Science Translational Medicine. 2015 Jul 22; 7(297):297Ir1. Doi: 10.1126/scietranslmed.aac9461. PMCID: Not Applicable.
407. Li HW, Andreola G, Carlson AL, Shao S, Lin CP, Zhao G, Sykes M. Rapid Functional Decline of Activated and Memory Graft-versus-Host-Reactive T Cells Encountering Host Antigens in the Absence of Inflammation. Journal of Immunology. 2015 Aug 1; 195(3): 1282-92. Doi: 10.4049/jimmunol.1401511. Epub 2015 Jun 17. PMCID: PMC4506852.
406. Sykes M. Immune tolerance in recipients of combined haploidentical bone marrow and kidney transplantation. Bone Marrow Transplantation. 2015 Jun; 50 Supple 2:S82-6. Doi: 10.1038/bmt.2015.102. PMCID: PMC4968035
405. Weiner J, Duran-Struuck R, Zitsman J, Buhler L, Sondermeijer H, McMurchy A, Levings M, Sykes M, Griesemer A. Restimulation After Cryopreservation and Thawing Preserves the Phenotype and Function of Expanded Baboon Regulatory T Cells. Transplantation Direct. February 2015, Volume 1 - Issue 1, p. 1-7. doi: 10.1097/TXD.0000000000000511
404. Zuber J, Rosen S, Shonts B, Sprangers B, Savage T, Richman S, Yang S, Lau S, DeWolf S, Vlad G, Zorn E, Wong W, Emond J, Martinez M, Kato T, Sykes, M. Macrochimerism in intestinal transplantation: association with lower rejection rates and multivisceral transplants, without GVHD. American Journal of Transplantation. 2015 Oct 15(10):2691-703 doi: 10.1111/ajt. 13325. Epub 2015 May 18. PMCID: PMC4575629.
403. Buchan S, Manzo T, Flutter B, Rogel A, Edwards N, Zhang L, Sivakumaran S, Ghorashian S, Carpenter B, Bennett C, Freeman G, Sykes M, Croft M, Al-Shamkhani A, Chakraverty R. OX40- and CD27-mediated co-stimulation synergize with anti-PD-L1 blockade by forcing exhausted CD8+ T cells to exit quiescence. Journal of Immunology. 2015 Jan 1: 194(1):125-33. Doi:10.4049/jimmunol. 1401644. PMCID: PMC4272895.
402. Sykes, M. Introduction of David H. Sachs, MD, Recipient of the 2014 Medawar Prize. Transplantation. 2015 Feb; 99(2): 253-4. Doi: 10.1097/TP.0000000000000594.
401. Morris H, De Wolf S, Robins H, Sprangers B, Locascio S, Shonts B, Kawai T, Wong W, Yang S, Zuber J, Shen Y, Sykes M. Tracking donor-reactive T cells: evidence for clonal deletion in tolerant kidney transplant patients. (Note: accompanied by FOCUS Article “I spy alloreactive T Cells” by Maria-Luisa Alegre.) Science Translational Medicine 7, 272ra10 (2015). PMCID: PMC4360892
400. Kawai T, Sachs DH, Sprangers B, Spitzer T, Saidman S, Zorn E, Tolkoff-Rubin N, Preffer F, Crisalli K, Gao B, Wong W, Morris H, LoCascio S, Sayre P, Shonts B, Williams W, Smith R, Colvin R, Sykes M, Cosimi A. Long-Term Results in Recipients of Combined HLA-Mismatched Kidney and Bone Marrow Transplantation Without Maintenance Immunosuppression. American Journal of Transplantation. 2014 July; 14(7); 1599-611. doi: 10.1111/ajt.12731. PMID: 24903438 PMCID: PMC4228952
399. Li H, Yang YG, Sykes M. Thymic education of human T cells and regulatory T cell development in humanized mice. In: Humanized Mice for HIV Research; Poluektova LY, Garcia-Martinez JV, Koyanagi Y, Manz MG, Tager AM (Ed.), New York, NY, Springer Science+Business Media; 2014; 10: 127-140
398. Kalscheuer H, Onoe T, Dahmani A, Holzl M, Yamada K, Sykes M. Xenograft tolerance and immune function of human T cells developing in pig thymus xenografts. Journal of Immunology, 2014 Apr 1;192(7):3442-50. doi: 10.4049/jimmunol.1302886. PMID: 24591363. PMCID: PMC3983999
397. Sykes M. Transplantation Immunology. In: The Cecil Text Book of Medicine, 25th Edition. (Eds), Goldman L, Ausiello, D. Philadelphia, PA; Saunders Elsevier; 2016. Vol. 1. Pp. 236-240
396. Sykes M. Transplantation: Moving to the Next Level. Immunological Reviews; 2014. 2014 Mar;258(1):5-11. doi: 10.1111/imr.12161. PMID: 24517422. PMCID: PMC4038030.
395. Griesemer A, Yamada K, Sykes M. Xenotransplantation: Immunological hurdles and progress toward tolerance. Immunological Reviews; 2014 Mar;258(1):241-58. doi: 10.1111/imr.12152. PMID: 24517437. PMCID: PMC4023346
394. Haspot F, Li HW, Lucas CL, Fehr T, Beyaz S, Sykes M. Allospecific rejection of MHC class I-deficient bone marrow by CD8 T cells. American Journal of Transplantation, 2014 Jan 14(1): 49-58. doi: 10.1111/ajt.12525. PMID: 24304495. PMCID: PMC4045013
393. Sachs DH, Kawai T, Sykes M. Induction of Tolerance Through Mixed Chimerism. In: Turka L, Wood K, editors. Cold Spring Harbor Perspectives; 2013. 2014 Jan 1;4(1):a015529. doi: 10.1101/cshperspect.a015529.
392. Kawai T, Sachs DH, Sykes M, Cosimi AB, for the Immune Tolerance Network. HLA mismatched renal transplantation without maintenance immunosuppression-an update. Letter to the Editor. May 9, 2013 N Engl J Med 2013; 368:1850-1852. PMID: 23656665 PMC3760499
391. Sykes M, Wood K, Sachs DH. Transplantation Immunology. In: Paul WE, editor. Fundamental Immunology (7th edition). Philadelphia, PA: Lippincott Williams & Wilkins Publishers; 2013. 46: 1154-1199
389. Sykes M. Transplantation Immunology. In: The Cecil Text Book of Medicine, 24th Edition. (Eds), Goldman L, Ausiello, D. Philadelphia, PA; Saunders Elsevier; 2012;48:235-239.
388. Li HW, Sachs J, Pichardo C, Bronson R, Zhao G, Sykes M. Nonalloreactive T cells prevent donor lymphocyte infusion-induced graft-versus-host disease by controlling microbial stimuli. J Immunol. 2012 Dec 15;189(12):5572-81. doi: 10.4049/jimmunol.1200045. Epub 2012 Nov 7. PubMed PMID: 23136200; PubMed Central PMCID: PMC3524834.
387. Wang H, Yang Y, Wang G, Wang S, Yeap BY, Sykes M, Yang YG. Donor bone marrow-derived T cells inhibit GVHD induced by donor lymphocyte infusion in established mixed allogeneic hematopoietic chimeras. PLoS One.2012;7(10):e47120.doi:10.1371/journal.pone.0047120. Epub 2012 Oct 15. PMCID:3471915.
386. Li H, Sykes M. Emerging concepts in haematopoietic cell transplantation. Nat Rev Immunol. 2012 May 25;12(6):403-16. doi: 10.1038/nri3226. PMID: 22627859 PMCID: PMC4006975
384. Kalscheuer H, Danzl N, Onoe T, Faust T, Winchester R, Goland R, Greenberg E, Spitzer TR, Savage DG, Tahara H, Choi G, Yang YG, Sykes M. A model for personalized in vivo analysis of human immune responsiveness. Sci Transl Med. 2012 Mar 14;4(125):125ra30. doi: 10.1126/scitranslmed.3003481. PubMed PMID: 22422991. NIHMS455065. PMCID: PMC3697150
381. Onoe T, Kalscheuer H, Danzl N, Chittenden M, Zhao G, Yang YG, Sykes M. Human natural regulatory T cell development, suppressive function and post-thymic maturation in a humanized mouse model. J Immunol. 2011 Oct 1;187(7):3895-903. Epub 2011 Aug 29. NIHMS 316848. PMCID: 3201793
379. Strober S, Spitzer TR, Lowsky R, Sykes M. Translational studies in hematopoietic cell transplantation: Treatment of hematologic malignancies as a stepping stone to tolerance induction. Semin Immunol. 2011 Aug;23(4):273-81. Epub 2011 Jun 25. PMCID: 3201788
378. Levesque V, Bardwell PD, Shimizu I, Haspot F., Benichou G, Yeap BY, Sykes M. B Cell-Dependent Memory T Cells Impede Nonmyeloablative Mixed Chimerism Induction in Presensitized Mice. AJT 2011. Am J Transplant. 2011 Nov;11(11):2322-31. doi: 10.1111/j.1600-6143.2011.03683.x. Epub 2011 Aug 10. PMCID: PMC3816363
377. Fujisaki J, Wu J, Carlson AL, Silberstein L, Putheti P, Larocca R, Gao W, Saito TI, Lo Celso C, Tsuyuzaki H, Sato T, Cote D, Sykes M, Strom TB, Scadden DT, Lin CP. In vivo imaging of Treg cells providing immune privilege to the haematopoietic stem-cell niche. Nature. 2011 Jun 8;474(7350):216-9. doi: 10.1038/nature10160. PMCID 3725645
376. Lucas C, Workman CJ, Beyaz S, LoCascio S, Zhao G, Vignali DAA, Sykes M. LAG-3, TGF-β, and cell-intrinsic PD-1 inhibitory pathways contribute to CD8 but not CD4 T-cell tolerance induced by allogeneic BMT with anti-CD40L. Blood. 2011 May 19;117(20):5532-40 PMCID: 3109721
375. Farris AB, Taheri D, Kawai T, Fazlollahi L, Wong W, Tolkoff-Rubin N, Spitzer TR, Lafrate AJ, Preffer FI, LoCascio SA, Sprangers B, Saidman S, Smith RN, Cosimi AB, Sykes M, Sachs DH, Colvin RB. Acute renal endothelial injury during marrow recovery in a cohort of combined kidney and bone marrow allografts. Am J Transplant. 2011 Jun 10. doi: 10.1111/j.1600-6143.2011.03572 PMCID: 3128680
374. Andreola G, Chittenden M, Shaffer J, Cosimi A.B, Kawai T, Cotter P, LoCascio SA, Morokata T, Dey BR, Tolkoff-Rubin NT, Preffer F, Bonnefoix T, Kattleman K, Spitzer TR, Sachs DH, Sykes M. Mechanisms of Donor-Specific Tolerance in Recipients of Haploidentical Combined Bone Marrow/Kidney Transplantation. Am J Transplant. 2011 Jun;11(6):1236-1247. doi: 10.1111/j.1600-6143.2011.03566 PMCID: 3140222
373. Spitzer TR, Sykes M, Tolkoff-Rubin N, Kawai T, McAfee SL, Dey BR, Ballen K, Delmonico F, Saidman S, Sachs DA, Cosimi AB. Long Term Follow-Up of Recipients of Combined HLA-matched Bone Marrow and Kidney Transplantation for Multiple Myeloma with End-Stage Renal Disease. Transplantation. 2011 Mar 27;91(6):672-6 PMCID: 3232059
371. LoCascio SA, Morokata T, Chittenden M, Preffer F, Dombrowski DM, Andreola G, Crisalli K, Kawai T, Saidman SL, Spitzer TR, Tolkoff-Rubin N, Cosimi AB, Sachs D, Sykes M. Mixed Chimerism, Lymphocyte Recovery and Evidence for Early Donor-Specific Unresponsiveness in Patients Receiving CKBMT to Induce Tolerance. Transplantation. 2010 Dec 27;90(12):1607-15. PMCID: 3059844
370. Griesemer A, Liang F, Hirakata A, Hirsh E, Lo D, Okumi M, Sykes M, Yamada K, Huang CA, Sachs DH. Occurrence of specific humoral non-responsiveness to swine antigens following administration of GalT-KO bone marrow to baboons. Xenotransplantation. 17 (4):300-312, 2010. PMCID: 2942069
368. Flutter B, Edwards N, Fallah-Arani F, Henderson S, Chai JG, Sivakumaran S, Ghorashian S, Bennett CL, Freeman GJ, Sykes M, Chakraverty R. Nonhematopoietic antigen blocks memory programming of alloreactive CD8+ T cells and drives their eventual exhaustion in mouse models of bone marrow. J Clin Invest. 2010 Nov 1;120(11):3855-68. doi: 10.1172/JCI41446. Epub 2010 Oct 18. PMCID: 2964967
367. Saito TI, Li H, Sykes M. Invariant natural killer T cells are required for antitumor responses induced by host-versus-graft responses. J. Immunol. 2010. Aug 15;185(4):2099-105. PMCID: 3111022
366. Saito TI, Fujisaki J, Carlson AL, Lin CP, Sykes M. Persistence of donor-derived protein in host myeloid cells after induced rejection of engrafted allogeneic bone marrow cells. Exp. Hematol. 2010, April;38(4):333-9.Epub 2010 Feb 16. PMC3965294
364. Onoe T, Kalscheuer H, Chittenden M, Zhao G, Yang YG, Sykes M. Homeostatic expansion and phenotypic conversion of human T cells depend on peripheral interactions with APCs. J Immunol. 2010 Jun 15;184(12):6756-65. PMCID: 3086709
363. Sykes M. Immune Evasion by Chimeric Trachea. New Engl. J. Med., 2010;362(2): 172-174. PMID: 20071709 PMCID N/A
362. Nikolic B, Onoe T, Takeuchi Y, Khalpey Z, Primo V, Leykin I, Smith RN and Sykes M. Distinct requirements for achievement of allotolerance versus reversal of autoimmunity via non-myeloablative mixed chimerism induction in NOD mice. Transplantation, 2010; 89:23-32. PMCID: 3043373
361. Fehr T, Lucas C, Kurtz J, Onoe T, Zhao G, Hogan T, Vallot C, Rao A and Sykes M. A CD8 T cell-intrinsic role for the calcineurin-NFAT pathway for tolerance induction in vivo. Blood 2010; 115: 1280-1287. PMCID: 2826238.
360. Mollov JL, Haspot F, Lucas C, Gaspar C, Guzman A and Sykes M. Recipient dendritic cells, but not B cells, are required antigen-presenting cells for peripheral alloreactive CD8+ T cell tolerance. Am J Transplant, 2010; 10(3): 518-526. PMID: 20121730 PMCID: PMC4215806.
358. Griesemer AD, Hirakata A, Shimizu A, Moran S, Tena A, Iwaki H, Ishikawa Y, Schule P, Arn JS, Robson SC, Fishman JA, Sykes M, Sachs DH, Yamada K. Results of gal-knockout porcine thymokidney xenografts. Am. J. Transplant. 2009; 9(12): 2669-2678. PMCID: 2801602
357. Cozzi E, Tallacchini M, Flanagan EB, Pierson RN, III, Sykes M and Vanderpool HY. The International Xenotransplantation Association consensus statement on conditions for undertaking clinical trials of porcine islet products in type 1 diabetes--chapter 1: Key ethical requirements and progress toward the definition of an international regulatory framework. Xenotransplantation, 2009; 16: 203-214. PMID: 19799760 PMCID N/A
356. Porcheray F, Wong W, Saidman S, De Vito J, Girouard T, Chittenden M, Shaffer J, Tolkoff-Rubin N, Dey B, Spitzer T, Colvin R, Cosimi A, Kawai T, Sachs D, Sykes M and Zorn E. B cell immunity in the context of T cell tolerance after combined kidney and bone marrow transplantation in humans. Am. J. Transplant. 2009; 9: 2126-2135. PMCID:2837587
354. Habiro K, Sykes M, Yang YG. Induction of human T cell tolerance to pig xenoantigens via thymus transplantation in mice with an established human immune system. Am. J. Transplant. 2009; 9(6):1324-1329. PMCID: 2752337
353. Wang H, Asavaroengchai W, Wang MG, Wang S, Sykes M, Yang YG. Paradoxical effects of IFN-g in graft-vs.-host (GVH) disease reflect promotion of lymphohematopoietic GVH reactions and inhibition of epithelial tissue injury. Blood 2009; 113: 3612-19. PMCID: 2668848
352. Kurtz J, Raval F, Vallot C, Der J, Sykes M. CTLA-4 on alloreactive CD4 T cells interacts with recipient CD80/86 to promote tolerance. Blood. 2009; 113: 3475 - 3484. PMCID: 2668856
351. Sachs DH, Sykes M, Yamada K. Achieving tolerance in pig-to-primate xenotransplantation: Reality or fantasy. Transplant. Int. 2009; 21(2):101-5. PMCID: 19059481
349. Sykes M. Mechanisms of Tolerance. In Thomas’ Hematopoietic Cell Transplantation (4th Edition); Appelbaum FR, Forman SJ, Negrin RS and Blume KG (Eds.), Oxford, UK, Blackwell Publishing. 2009; 15: 188-207. PMCID: N/A
348. Fudaba Y, Onoe T, Chittenden M, Shimizu A, Shaffer J, Bronson R, Sykes M. Abnormal regulatory and effector T cell function predispose to autoimmunity following xenogeneic thymic transplantation. J. Immunol. 2008; 181: 7649 - 7659. PMCID: 2673578
347. Chakraverty R, Flutter B, Fallah-Arani F, Eom H-S, Means T, Andreola G, Schwarte S, Buchli J, Cotter P, Zhao G, Sykes M. The host environment regulates the function of CD8+ graft-versus-host-reactive effector cells J. Immunol. 2008; 181:6820-6828. PMCID: 18981100
345. Haspot F, Bardwell PD, Zhao G, Sykes M. High antigen levels do not preclude B cell tolerance induction to α1,3Gal via mixed chimerism. Xenotransplantation. 2008; 15:313-320. PMCID: 2633101
344. Fehr T, Wang S, Haspot F, Kurtz J, Blaha P, Hogan T, Chittenden M, Wekerle T, Sykes M. Rapid, deletional peripheral CD8 T cell tolerance induced by allogeneic bone marrow: role of donor class II MHC and B cells. J Immunol. 2008; 181:4371-4380. PMCID: 2628539
343. Koporc Z, Pilat N, Nierlich P, Blaha P, Bigenzahn S, Pree I, Selzer E, Sykes M, Muehlbacher F and Wekerle T. Murine mobilized peripheral blood stem cells have a lower capacity than bone marrow to induce mixed chimerism tolerance. Am. J. Transplant. Am. J. Transplant. 2008; 8:2025-36. PMCID: 18828766
341. Shimizu I, Fudaba Y, Shimizu A, Yang Y-G, Sykes M. Comparison of human T cell repertoire generated in xenogenic porcine and human thymus grafts. Transplantation. 2008; 86: 601-610. PMCID: 26806891
340. Fehr T, Haspot F, Mollov J, Chittenden M, Hogan T, Sykes M. Alloreactive CD8 T cell tolerance requires recipient B cells, dendritic cells and MHC class II. J Immunol. 2008; 181: 165-173. PMCID: 18566381
339. Ting DT, Spitzer TR, Chaudhary A, Muzikansky A, Colby C, Power K, McAfee S, Ballen K, Attar E, Saidman SL, Preffer F, Sykes M, Dey BR. Clinical outcomes of late rather than early full-donor chimerism in patients with advanced lymphomas receiving nonmyeloablative allogeneic hematopoietic SCT. Bone Marrow Transplant. 2008; 42: 329-335. PMCID: 18587439
338. Haspot F, Fehr T, Gibbons G, Zhao G, Hogan T, Honjo T, Freeman GJ, Sykes M. Peripheral deletional tolerance of alloreactive CD8 but not CD4 T cells is dependent on the PD-1/PD-L1 pathway. Blood. 2008; 112: 2149-55. PMCID: PMC2518911.
337. Sykes M, Wood K, Sachs DH. Transplantation Immunology. In: Fundamental Immunology (6th edition); Paul WE (Ed.), Philadelphia, PA, Lippincott Williams & Wilkins; 2008; 44: 1426-1489. PMCID: N/A
333. Tonomura N, Habiro K, Shimizu A, Sykes M, Yang Y-G. Antigen specific human T cell responses and T cell-dependent production of human antibodies in a humanized mouse model. Blood. 2008 ; 111: 4293-4296. PMCID: 22887281
331. Gibbons C and Sykes M. Manipulating the immune system for anti-tumor responses and transplant tolerance via mixed chimerism. Immunol. Rev. 2008; 223: 334-360. PMCID: 2680695
330. Sykes M, 2007 IXA Presidential Address. Progress toward an ideal source animal: opportunities and challenges in a changing world. Xenotransplantation. 2008; 15: 7-13. PMCID: 18333908
329. Kawai T, Cosimi AB, Spitzer TR, Tolkoff-Rubin N, Suthanthiran M, Saidman S, Shaffer J, Preffer F, Ding R, Sharma V, Fishman J, Dey BR, Ko D, Hertl M, Goes N, Wong W, Williams W, Colvin RB, Sykes M, and Sachs DH. HLA-mismatched renal transplantation without maintenance immunosupression. New Engl. J. Med. 2008; 358(4): 353-361. PMCID: 18216355
327. Sykes M. Immune tolerance: mechanisms and application in clinical transplantation. J Intern Med. 2007; 262: 288-310.
325. Kawahara T, Rodriguez-Barbosa J-I, Zhao Y, Zhao G, Sykes M. Global unresponsiveness as a mechanism of natural killer cell tolerance in mixed xenogeneic chimeras. Am. J. Transplant. 2007; 7: 2090-2097.
323. Dey BR, Shaffer J, Yee AJ, McAfee S, Caron M, Power K, Ting DT, Colby C, Preffer F, Ballen K, Attar E, Saidman S, Tarbell N, Sachs DH, Sykes M, Spitzer TR. Comparison of outcomes after transplantation of peripheral blood stem cells versus bone marrow following an identical nonmyeloablative conditioning regimen. Bone Marrow Transplant. 2007; 40(1):19-27.
322. Hongo D, Hadidi S, Damrauer S, Garrigue V, Kraft D, Sachs DH, Nikolic B and Sykes M. Porcine thymic grafts protect human thymocytes from HIV-1-induced destruction. J Infect Dis 2007; 196(6): 900-910.
321. Shaffer J, Villard J, Means TK, Dombkowski D, Dey BR, McAfee S, Ballen KK, Saidman S, Preffer FI, Sachs DH, Spitzer TR, and Sykes M. Regulatory T cell recovery in recipients of haploidentical non-myeloablative hematopoietic cell transplantation with a humanized anti-CD2 mAb, MEDI-507, with or without fludarabine. Exp. Hemat. 2007; 35(7): 1140-1152.
320. Pree I, Bigenzahn S, Fuchs D, Koporc Z, Nierlich P, Winkler C, Brandacher G, Sykes M, Muehlbacher F, Langer F, and Wekerle T. CTLA4Ig promotes the induction of hematopoietic chimerism and tolerance independently of Indoleamine-2,3-dioxygenase. Transplantation 2007; 83:663-667.
319. Yamada K, Griesemer A, Sykes M and Sachs DH. Contransplantation of vasculariazed thymus and kidney from GalT-KO pigs to baboons. Xenotranplantation 2007; 14: 186-189.
318. Yang Y and Sykes M. Xenotransplantation - Current status and a perspective on the future. Nat. Rev. Immunol. 2007; 7(7):519-531.
316. Ide K, Wang H, Tahara H, Liu J, Wang X, Asahara T, Sykes M, Yang Y, Ohdan H. Role for CD47-SIRPα signaling in xenograft rejection by macrophages. Proc. Nat. Acad. Sci. USA 2007; 104(12):5062-5066.
315. Chakraverty R and Sykes M. The role of antigen-presenting cells in triggering GVHD and GVL. Blood. 2007; 110:-9-17. PMCID: 1896131
313. Koyama I, Nadazdin O, Boskovic S, Ochiai T, Smith RN, Sykes M, Sogawa H, Murakami T, Strom T, Colvin RB, Sachs DH, Benichou G, Cosimi AB, Kawai T. Depletion of CD8 memory T cells for induction of tolerance of a previously transplanted kidney allograft. Am. J. Transplant. 2007; 7(5):1055-1061.
312. Yang Y-G and Sykes M. Tolerance in xenotransplantation. Curr. Opin. in Organ Transplant. 2007;12: 169-175.
308. Asavaroengchai W, Wang H, Wang S, Wang L, Bronson R, Sykes M, Yang Y-G. An essential role for IFN-γ in regulation of alloreactive CD8 T cells following allogeneic heamatopoietic cell transplantation. Biol Blood Marrow Transplant. 2007; 13(1): 46-55.
307. Shimizu I, Kawahara T, Haspot F, Bardwell PD, Carroll MC, Sykes M. B-cell extrinsic CR1/CR2 promotes natural antibody production and tolerance induction of anti-αGal-producing B-1 cells. Blood. 2007: 109(4): 1773-1781.
306. Wang H, VerHalen J, Madariaga ML, Xiang S, Wang S, Lan P, Oldenborg P-A, Sykes M, Yang Y-G. Attenuation of phagocytosis of xenogeneic cells by manipulating CD47. Blood. 2007; 109(2):836-842.
305. Sykes M. Transplantation Immunology. In: The Cecil Text Book of Medicine, 23rd Edition. (Eds), Goldman L, Ausiello, D; Saunders. New York, NY; Saunders Elsevier; 2007;46:277-282.
302. Sykes M, Cozzi E, d’ Apice A, Pierson R, O’Connell P, Cowan P, Dorling A, Hering B, Leventhal J, Rees M, Sandrin M. Clinical trial of islet xenotransplantation in Mexico. Xenotransplantation. 2006;13(5):371-372 .
301. Chakraverty R, Cote D, Buchli J, Cotter P, Hsu R, Zhao G, Sachs T, Pitsilldes C, Bronson R, Means T, Lin C, Sykes M. An inflammatory checkpoint regulates recruitment of graft-versus-host reactive T cells to peripheral tissues. J. Exp. Med. 2006;203(8):2021-2031.
299. Saito TI, Rubio MT, Sykes M. Clinical relevance of recipient leukocyte infusion as anti-tumor therapy following nonmyeloablative allogeneic hematopoietic cell transplantation. Exp. Hemat. 2006;34(9):1270-1276.
297. Sykes M and Cozzi E. Xenotransplantation of pig islets into Mexican children: Were the fundamental ethical requirements to proceed with such a study really met? Eur. J. Endocrinol. 2006;154(6):921-922.
296. Fudaba Y, Spitzer TR, Shaffer JM, Kawai T, Fehr T, Delmonico FL, Preffer FI, Tolkoff-Rubin, Dey BR, Saidman SL, Kraus A, Bonnefoix T, McAfee S, Power K, Kattelman K, Colvin RB, Sachs DH, Cosimi AB Sykes M. Myeloma responses and tolerance following combined kidney and non-myeloablative marrow transplantation in vivo and in vitro analyses. Am. J. Transplant. 2006;6:2121-2133.
295. Chakraverty R, Eom H-S, Sachs J, Buchli J, Cotter P, Hsu R, Zhao G, Sykes M. Host MHC Class II+ antigen-presenting cells and CD4 cells are required for CD8 mediated graft-versus-leukemia responses following delayed donor leukocyte infusions. Blood. 2006;108(6):2106-2113.
294. Rubio MT, Zhao G, Buchli J, Chittenden M, Sykes M. Role of indirect allo- and autoreactivity in anti-tumor responses induced by recipient leukocyte infusions (RLI) in mixed chimeras prepared with nonmyeloablative conditioning. Clin Immunol. 2006;120(1):33-44.
293. Ito H, Takeuchi Y, Shaffer JM, Sykes M. Anti-CD40L mAb can replace anti-CD4 mAb for the non-myeloablative induction of mixed xenogeneic chimerism. Transplantation 2006;82(2):251-257.
292. Mapara MY, Leng C, Kim YM, Bronson R, Lokshin A, Luster AD, Sykes M. Expression of chemokines in GVHD target organs is influenced by conditioning and genetic factors and amplified by GVHR. Biol. Blood Marrow Transplant. 2006; 12(6):623-634.
289. Shimizu I, Smith RN, Zhao G, Medof E, Sykes M. Decay accelerating factor prevents acute humoral rejection induced by low levels of anti-αGal natural antibodies. Transplantation 2006;81(1):95-100.
288. Xu Y, Yang Y-G, Ohdan H, Ryan D, Harper D, Wu C, Kruger-Grey H, Thall A, Awwad M, Sykes M. Characterization of anti-gal antibody-producing cells of baboons and humans. Transplantation. 2006;81(6);940-948.
286. Fehr T, Bardwell PD, Sykes M. Use of skin grafting to demonstrate tolerance before kidney transplantation without immunosuppression in the recipient of a previous bone marrow transplant. Transplantation. 2005;80(9):1359-1360.
283. Bardwell PD, Ohdan H, Sykes M. B cell tolerance and xenotransplantation. Curr. Opin. in Organ Transplant. 2005;10(3)252-258.
282. Rubio MT, Means TK, Chakraverty R, Shaffer JM, Fudaba Y, Chittenden M, Luster AD, Sykes M. Maturation of human monocyte-derived dendritic cells (MoDCs) in the presence of Prostaglandin E2 optimizes CD4 and CD8 T cell-mediated responses to protein antigens: role of PGE2 in chemokine and cytokine expression by MoDCs. Int Immunol. 2005;17(12):1561-1572.
281. Fehr T, Takeuchi Y, Kurtz J, Wekerle T, Sykes M. Early regulation of CD8 T cell alloreactivity by CD4(+)CD25(- )T cells in recipients of anti-CD154 antibody and allogeneic BMT is followed by rapid peripheral deletion of donor-reactive CD8(+) T cells, precluding a role for sustained regulation. Eur. J. Immunol. 2005;35:(9)2679-2690.
280. Eom HS, Rubio MT, Means TK, Luster AD, Sykes M. T cell P/E-selectin ligand α(1,3)fucosylation is not required for GVHD induction. Exp. Hemat. 2005;33(12):1564-1573.
276. Kawahara T, Shimizu I, Ohdan H, Zhao G, Sykes M. Differing mechanisms of early and late B cell tolerance induced by mixed chimerism. Am. J. Transplant. 2005;5(12):2821-2829.
275. Sykes M, Nikolic B. Treatment of severe autoimmune disease by stem-cell transplantation. Nature 2005;435:620-627.
274. Rubio MT, Saito TI, Kattleman K, Zhao G, Buchli J, Sykes M. Mechanisms of the anti-tumor responses and host-versus graft reactions induced by recipient leukocyte infusions in mixed chimeras prepared with nonmyeloablative conditioning: a critical role for recipient CD4+ T cells and recipient leukocyte infusion-derived interferon-gamma-producing CD8+ T Cells. J. Immunol. 2005;175(2)665-676.
269. Dey BR, McAfee S, Colby C, Cieply K, Caron M, Saidman S, Preffer FI, Shaffer JM, Tarbell N, Sackstein R, Sachs DH, Sykes M, Spitzer TR. Anti-tumor response despite loss of donor chimerism in patients treated with nonmyeloablative conditioning and allogeneic stem cell transplantation. Br. J. of Hematol. 2005;128:351-359.
268. Yamada K, Yazawa K, Shimizu A, Iwanaga T, Hisashi Y, Nuhn M, O’Malley P, Nobori S, Vagefi PA, Patience C, Fishman J, Cooper DKC, Hawley RJ, Greenstein J, Schuurman HJ, Awwad M, Sykes M, Sachs DH. Marked prolongation of porcine renal xenograft survival in baboons through the use of Gal-T knock out donors and the co-transplantation of vascularized thymic tissue. Nat. Med. 2005;11(1):32-34..
264. Sykes M, d'Apice A, Sandrin M. IXA Ethics Committee: Position paper of the Ethics Committee of the International Xenotransplantation Association. Transplantation 2004;78:1101-1107.
263. Kawai T, Sogawa H, Boskovic S, Abrahamian G, Smith R-N, Wee S-L, Andrews D, Nadazdin O, Koyama I, Sykes M, Winn HJ, Colvin RB, Sachs DH and Cosimi AB. CD154 Blockade for induction of mixed chimerism and prolonged renal allograft survival in nonhuman primates. Am. J. Transplantation 2004;4(9):1391-1398.
262. Sykes M, Sandrin M, and Cozzi E. International cooperation on xenotransplantation. Nat. Med. 2004;10(2):119.
259. Kurtz J, Wekerle T, Sykes M. Tolerance in mixed chimerism – a role for regulatory cells? Trends in Immunol. 2004;25(10)518-523.
257. Kurtz J, Shaffer JM, Lie A, Anosova N, Benichou G, Sykes M. Mechanisms of early peripheral CD4 cell tolerance induction by anti-CD154 monoclonal antibody and allogeneic bone marrow transplantation: Evidence for anergy and deletion, but not regulatory cells. Blood 2004;103(11):4336-4343.
256. Sykes M, Sandrin M, Cozzi E: Ethics committee of the International Xenotransplantation Association. International Cooperation on Xenotransplantation. Nat. Med. 2004;10(2):119.
255. Lan P, Wang L, Diouf B, Eguchi H, Su H, Bronson R, Sachs DH, Sykes M, Yang Y-G. Induction of human T cell tolerance to porcine xenoantigen through mixed hematopoietic chimerism. Blood 2004;103(10):3964-3969.
253. Nikolic B, Takeuchi Y, Leykin I, Smith RN, Sykes M. Mixed hematopoietic chimerism allows cure of autoimmune diabetes through allogeneic tolerance and reversal of autoimmunity. Diabetes 2004;53(2)376-383.
252. Ito H, Takeuchi Y, Shaffer JM, Sykes M. Local irradiation enhances congenic donor pluripotent hematopoietic stem cell engraftment similarly in irradiated and non-irradiated sites. Blood 2004;103(5)1949-1954.
251. Mapara MY, Sykes M. Biology of neoplasia – Tolerance and cancer: mechanisms of tumor evasion and strategies for breaking tolerance. J. Clin. Oncol. 2004;22(6)1136-1151.
250. Takeuchi Y, Ito H, Kurtz J, Wekerle T, Ho L, Sykes M. Earlier low dose TBI or DST overcomes CD8+ T cell-mediated alloresistance to allogeneic marrow in recipients of anti-CD40L. Am. J. Transplantation 2004;4:31-40.
249. Kim Y-M, Mapara MY, Down JD, Johnson KW, Boisgerault F, Akiyama Y, Benichou G, Pelot M, Zhao G, Sykes M. Graft-versus-host (GVH)-reactive donor CD4 cells can induce T cell-mediated rejection of the donor marrow in mixed allogeneic chimeras prepared with nonmyeloablative conditioning. Blood 2004;103:732-739.
247. Yang Y-G, Wood JC, Lan P, Wilkinson, Sykes M, Fishman JA, Patience C. Mouse retrovirus mediates porcine endogenous retrovirus transmission into human cells in long-term human-porcine chimeric mice. J. Clin. Invest. 2003;114:695-700.
246. Sykes M. JAKing up immunosuppression [Editorial – News & Views]. Nat. Med. 2003;12:1458-1459.
245. Sykes M, Sandrin M, D'Apice A: Ethics Committee of the International Xenotransplantation Association. Guidelines for Xenotransplantation. New Engl. J. Med. 2003;349:1294-1295.
244. Daly A, McAfee S, Dey BR, Colby C, Schulte L, Yeap B, Sackstein R, Tarbell NF, Sachs DH, Sykes M, Spitzer TR. Nonmyeloablative bone marrow transplantation: infectious complications in 65 recipients of HLA-identical and mismatched transplants. Biol. Blood Marrow Transplant. 2003;9:373-382.
242. Kawahara T, Ohdan H, Zhao G, Yang Y-G, Sykes M. Peritoneal Cavity B Cells Are Precursors Of Splenic IgM Natural Antibody-Producing Cells. J. Immunol. 2003;171:5406-5414.
241. Koenecke C, Shaffer JM, Alexander SI, Preffer FI, Dombkowski D, Saidman SL, Dey BR, McAffee S, Spitzer TR, Sykes M. NK cell recovery, chimerism, function and recognition in recipients of haploidentical hematopoietic cell transplantation following non-myeloablative conditioning using a humanized anti-CD2 mAb, Medi-507. Exp. Hematol. 2003;31:911-923.
239. Dey BR, McAfee S, Colby C, Sackstein R, Saidman S, Tarbell N, Sachs DH, Sykes M, Spitzer TR. Impact of prophylactic donor leukocyte infusions on mixed chimerism, graft-versus-host disease, and antitumor response in patients with advanced hematologic malignancies treated with nonmyeloablative conditioning and allogeneic bone marrow transplantation. Bio. Blood Marrow Transplant. 2003;9:320-329.
238. Rubio M-T, Kim Y-m, Sachs T, Mapara MY, Zhao G, Sykes M. Anti-tumor effect of donor marrow graft rejection induced by recipient leukocyte infusions in mixed chimeras prepared with nonmyeloablative conditioning: Critical role for recipient-derived IFN-γ. Blood 2003;102:2300-2307.
237. Kraus AB, Shaffer JM, Toh HC, Preffer FI, Dombkowski D, Saidman S, Colby C, George R, McAfee S, Sackstein R, Dey BR, Spitzer TR, Sykes M. Early host CD8 T-cell recovery and sensitized anti-donor IL-2-producing and cytotoxic T cell responses associated with marrow graft rejection following nonmyeloablative allogeneic bone marrow transplantation. Exp. Hematol. 2003;31:609-621.
236. Zhao Y, Ohdan H, Manilay JO, Sykes M. NK cell tolerance in mixed allogeneic chimeras. J. Immunol. 2003;170:5398-5405.
235. Mapara MY, Kim Y-M, Marx J, Sykes M. DLI-mediated GVL effects in mixed chimeras established with a nonmyeloablative conditioning regimen; extinction of GVL effects following conversion to full donor chimerism. Transplantation 2003;76:297-305.
234. Kurtz J, Lie A, Griffith M, Eysaman S, Shaffer JM, Anosova N, Turka L, Benichou G, Sykes M. Lack of role for CsA-sensitive or Fas pathways in the tolerization of CD4 T cells via BMT and anti-CD40L. Am. J. Transplant. 2003;3:804-816.
233. Kim Y-M, Sachs T, Asavaroengchai W, Bronson R, Sykes M. Graft-versus-host disease (GvHD) can be separated from graft-versus-lymphoma effects by controlling lymphocyte trafficking with FTY720. J. Clin. Invest. 2003;111:659-669.
232. Sykes M, d'Apice Anthony, Sandrin M. IXA Ethics Committee: Position paper of the Committee on Ethics of Xenotransplantation for the International Xenotransplantation Association. Xenotransplantation 2003;10:194-203.
231. Zhao Y, Rodriquez-Barbosa JI, Shimizu A, Swenson KG, Sachs DH, Sykes M. Despite efficient intrathymic negative selection of host-reactive T cells, autoimmune disease may develop in porcine thymus-grafted athymic mice: evidence for failure of regulatory mechanisms suppressing autoimmunity. Transplantation 2003;75:1832-1840.
229. Spitzer TR, McAfee S, Dey BR, Colby C, Hope J, Grossberg H, Preffer FI, Shaffer JM, Alexander SI, Sachs DH, Sykes M. Non-myeloablative haploidentical stem cell transplantation using anti-CD2 monoclonal antibody (MEDI-507) based conditioning for refractory hematologic malignancies. Transplantation 2003;75:1748-1751.
228. Sykes M, Auchincloss Jr. H, Sachs DH. Transplantation Immunology. In: Paul WE, editor. Fundamental Immunology (5th edition). Philadelphia, PA: Lippincott-Raven Publishers; 2003, pp. 1481-1555.
227. Rodriguez-Barbosa JI, Zhao Y, Houser S, Zhao G, Sykes M. Fetal porcine thymus engraftment, survival and CD4 reconstitution in αGal-KO mice is impaired in the presence of high levels of antibodies against αGal. Xenotransplantation 2003;10:24-40.
225. Ohdan H, Sykes M. B cell tolerance to xenoantigens. Xenotransplantation 2003;10:98-106.
210. Yang Y-G, Qi J, Wang MG, Sykes M. Donor-derived interferon γ separates graft-versus-leukemia effects and graft-versus host disease induced by donor CD8 T cells. Blood 2002;99:4207-4215.
208. Theodore PR, Simon AR, Warrens AN, Sackstein R, Sykes M. Porcine mononuclear cells adhere to human fibonectin independently of VLA-5: implications for donor-specific tolerance induction in xenotransplantation. Xenotransplantation 2002;9:277-289.
206. Spitzer TR, McAfee S, Sackstein R, Colby C, Dey BR, Saidman S, Preffer FI, Alexander S, Sachs DH, Sykes M. Mixed lymphohematopoietic chimerism and delayed donor leukocyte infusions following non-myeloablative conditioning and HLA-matched and mismatched donor bone marrow transplantation. In: Dicke KA & Keating A, editors. Proceedings: 10th Symposium Auto. Blood and Marrow Transplantation. Charlottesville, VA: Carden Jennings Publishing; 2002. pp. 321-332.
202. Kurtz J, Ito H, Wekerle T, Shaffer JM, Sykes M. Mechanisms involved in the establishment of tolerance through costimulatory blockade and BMT: Lack of requirement for CD40L-mediated signaling for tolerance or deletion of donor-reactive CD4+ cells. Am. J. Transplant. 2001;1:339-349.
199. Rodriguez-Barbosa JI, Zhao Y, Barth RN, Zhao G, Arn JS, Sachs DH, Sykes M. Enhanced CD4 reconstitution by grafting neonatal porcine tissue in alternative locations is associated with donor-specific tolerance and suppression of preexisting xenoreactive T cells: Transplantation 2001;72:1223-1231..
197. Mapara MY, Pelot M, Zhao G, Swenson K, Pearson D, Sykes M. Induction of stable long-term mixed hematopoietic chimerism following nonmyeloablative conditioning with T cell-depleting antibodies, cyclophosphamide, and thymic irradiation leads to donor-specific in vitro and in vivo tolerance. Biol. Blood Marrow Transplant. 2001;7:646-655.
195. Ohdan H, Swenson KG, Kitamura H, Yang Y-G, Sykes M. Tolerization of Gala1,3Gal-reactive B cells in pre-sensitized a1,3-galactosyltransferase-deficient mice by nonmyeloablative induction of mixed chimerism. Xenotransplantation 2001;8:227-238.
193. Ohdan H, Yang Y-G, Swenson KG, Kitamura H, Sykes M. T cell and B cell tolerance to Gala1,3Gal-expressing heart xenografts in a1,3-galatosyltransferase-deficient mice by non-myeloablative induction of mixed chimerism. Transplantation 2001;71:1532-1542.
190. Sykes M. Mixed chimerism and transplant tolerance. Immunity 2001;14:417-424.
189. Wekerle T, Kurtz J, Sayegh MH, Ito H, Wells A, Bensigner S, Shaffer JM, Turka LA, Sykes M. Peripheral deletion after bone marrow transplantation with costimulatory blockade has features of both activated-induced cell death and passive cell death. J. Immunol. 2001;166:2311-2316.
188. Ito H, Kurtz J, Shaffer JM, Sykes M. CD4 T cell-mediated alloresistance to fully MHC-mismatched allogeneic bone marrow engraftment is dependant on CD40-CD40 ligand interactions, and lasting T cell tolerance is induced by bone marrow transplantation with initial blockade of this pathway. J. Immunol. 2001;166:2970-2981.
185. Nikolic B, Cooke D, Zhao G, Sykes M. Both γδ T cells and NK cells inhibit the engraftment of xenogeneic rat bone marrow cells and induction of xenograft tolerance in mice. J. Immunol. 2001;166:1398-1404.
182. Zhao Y, Rodriguez-Barbosa JL, Zhao G, Shaffer JM, Arn JS, Sykes M. Maturation and function of mouse T cells with a transgenic TCR positively selected by highly disparate xenogeneic porcine MHC. Cell. Mol. Biol. 2001;1:217-228.
181. Nikolic B, Khan A, Sykes M. Induction of tolerance by mixed chimerism with non-myeloablative host conditioning: The importance of overcoming intrathymic alloresistance. Biol. Blood Marrow Transplant. 2001;17:144-153.
177. Ohdan H, Swenson KG, Kruger-Gray HS, Yang Y-G, Xu Y, Thall AD, Sykes M. Mac-1-negative B-1b phenotype of natural antibody-producing cells, including those responding to Gal α1,3 Gal epitopes in α 1, 3-galactosyltransferase deficient mice. J. Immunol. 2000 165:5518-5529.
173. Nikolic B, Zhao G, Swenson K, Sykes M. A novel application of cyclosporine A in non-myeloablative pre-transplant host conditioning for allogeneic BMT. Blood 2000;96:1166-1172.
172. Nikolic B, Lee S, Bronson RT, Grusby MJ, Sykes M. Th1 and Th2 mediate acute graft-versus-host disease, each with distinct end-organ targets. J. Clin. Invest. 2000;105:1289-1298.
171. Spitzer TR, McAfee S, Sackstein R, Colby C, Toh HC, Multani P, Saidman S, Weymouth D, Preffer FI, Poliquin C, Foley A, Cox B, Andrews D, Sachs DH, Sykes M. Intentional induction of mixed chimerism and achievement of anti-tumor responses after non-myeloablative conditioning therapy and HLA-matched donor bone marrow transplantation for refractory hematologic malignancies. Biol. Blood Marrow Transplant. 2000;6:309-320.
170. Wekerle T, Kurtz J, Ito H, Ronquillo JV, Dong V, Zhao G, Shaffer JM, Sayegh MH, Sykes M. Allogeneic bone marrow transplantation with costimulatory blockade induces macrochimerism and tolerance without cytoreductive host treatment. Nat. Med. 2000;6:464-469.
168. Yang Y-G, Chen AM, Garrett LJ, Sergio JJ, Theodore PR, Awwad M, VerHalen J, Bodine DM, Sachs DH, Sykes M. Development and analysis of transgenic mice expressing porcine hematopoietic cytokines: a model for achieving durable porcine hematopoietic chimerism across an extensive xenogeneic barrier. Xenotransplantation 2000;7:58-64.
161. Warrens AN, Simon AR, Theodore PR, Sachs DH, Sykes M. Cross-species compatibility of intercellular adhesion molecule-1 (CD54) with its ligands. Transplantation 2000;69:394-399.
160. Yang Y-G, Chen AM, Sergio JJ, Zhou Y, Sykes M. Role of antibody-independent complement activation in rejection of porcine bone marrow cells in mice. Transplantation 2000;69:163-165.
155. Manilay JO, Waneck GL, Sykes M. Levels of Ly-49 receptor expression are determined by the frequency of interactions with MHC ligands: evidence against receptor calibration to a “useful” level. J. Immunol. 1999;163:2628-2633.
154. Ohdan H, Yang Y-G, Shimizu A, Swenson KG, Sykes M. Mixed chimerism induced without lethal conditioning prevents T cell- and anti-Gala1,3Gal-mediated graft rejection. J. Clin. Invest. 1999;104:281-290.
148. Pelot MR, Pearson DA, Swenson K, Zhao G, Sachs J, Yang Y-G, Sykes M. Lymphohematopoietic graft-vs-host reactions can be induced without graft-vs-host disease in murine mixed chimeras established with a cyclophosphamide-based non-myeloablative conditioning regimen. Biol. Blood Marrow Transplant. 1999;5:133-143.
147. Dey BR, Yang Y-G, Preffer FI, Shimizu A, Swenson K, Dombkowski D, Sykes M. The fate of donor T-cell receptor transgenic T cells with known host antigen specificity in a graft-versus-host disease model. Transplantation 1999;68:141-149.
142. Sykes M, Preffer FI, McAfee S, Saidman SL, Weymouth D, Andrews D, Colby C, Sackstein R, Sachs DH, Spitzer TR. Mixed lymphohematopoietic chimerism and graft-vs-lymphoma effects are achievable in adult recipients following non-myeloablative therapy and HLA-mismatched donor bone marrow transplantation. Lancet 1999;353:1755-1759.
141. Nikolic B, Gardner JP, Scadden DT, Arn JS, Sachs DH, Sykes M. Normal development in porcine thymus grafts and specific tolerance of human T cells to porcine donor MHC. J. Immunol. 1999;162:3402-3407.
135. Yang Y-G, Dey BR, Sergio JJ, Pearson DA, Sykes M. Donor-derived Interferon g is required for inhibition of acute graft-versus-host disease by Interleukin 12. J. Clin. Invest. 1998;102:2126-2135.
134. Manilay JO, Waneck GL, Sykes M. Altered expression of Ly-49 receptors on natural killer cells developing in mixed allogeneic bone marrow chimeras. Int. Immunol. 1998;10:1943-1955.
131. Manilay JO, Pearson DA, Sergio JJ, Swenson KG, Sykes M. Intrathymic deletion of alloreactive T cells in mixed bone marrow chimeras prepared with a non-myeloablative conditioning regimen. Transplantation 1998;66:96-102.
129. Simon AR, Warrens AN, Yazzie NP, Seebach JD, Sachs DH, Sykes M. Cross-species interaction of porcine and human integrins with their respective ligands: implications for xenogeneic tolerance induction. Transplantation 1998;66:385-394.
128. Zhao Y, Swenson K, Sergio JJ, Sykes M. Pig MHC mediates positive selection of mouse CD4+ T cells with a mouse MHC-restricted TCR in pig thymus grafts. J. Immunol. 1998;161:1320-1326.
127. Wekerle T, Sayegh MH, Hill J, Zhao Y, Chandraker A, Swenson KG, Zhao G, Sykes M. Extrathymic T cell deletion and allogeneic stem cell engraftment induced with costimulatory blockade is followed by central T cell tolerance. J. Exp. Med. 1998;187:2037-2044.
125. Warrens AN, Simon AR, Theodore PR, Sachs DH, Sykes M. Function of porcine adhesion molecules in a human marrow microenvironment. Transplantation 1998;66:252-259.
124. Yang Y-G, deGoma E, Ohdan H, Bracey JL, Xu Y, Iacomini J, Thall AD, Sykes M. Tolerization of anti-gala1-3gal natural antibody-forming B cells by induction of mixed chimerism. J. Exp. Med. 1998;187:1335-1342.
123. Nikolic B, Lei H, Pearson DA, Sergio JJ, Swenson KG, Sykes M. Role of intrathymic rat class II+ cells in maintaining deletional tolerance in xenogeneic rat®mouse bone marrow chimeras. Transplantation 1998;65:1216-1224.
122. Dey BR, Yang Y-G, Szot GL, Pearson DA, Sykes M. IL-12 inhibits GVHD through a Fas-mediated mechanism associated with alterations in donor T cell activation and expansion. Blood 1998;91:3315-3322.
120. Zhao Y, Barth RN, Swenson K, Pearson DA, Sykes M. Functionally and phenotypically mature mouse CD8+ T cells develop in porcine thymus grafts in mice. Xenotransplantation 1998;5:99-104.
119. Sykes M, Szot GL, Swenson K, Pearson DA, Wekerle T. Separate regulation of peripheral hematopoietic and thymic engraftment. Exp. Hematol. 1998;26:457-465.
115. Yang Y-G, Sergio JJ, Sykes M. Engraftment of discordant xenogeneic swine bone marrow cells in immunodeficient mice. Xenotransplantation 1997;4:235-244.
114. Yang Y-G, Sergio JJ, Pearson DA, Szot GL, Shimizu A, Sykes M. Interleukin-12 preserves the graft-vs-leukemia effect of allogeneic CD8 T cells while inhibiting CD4-dependent graft-vs-host disease in mice. Blood 1997;90:4651-4660.
111. Nikolic B, Sykes M. Bone marrow chimerism and transplantation tolerance. Curr. Opin. Immunol. 1997;9:634-640.
110. Zhao Y, Sergio JJ, Swenson K, Arn JS, Sachs DH, Sykes M. Positive and negative selection of functional mouse CD4 cells by porcine MHC in pig thymus grafts. J. Immunol. 1997;159:2100-2107.
108. Sykes M, Szot GL, Swenson KA, Pearson DA. Induction of high levels of allogeneic hematopoietic reconstitution and donor-specific tolerance without myelosuppressive conditioning. Nat. Med. 1997;3:783-787.
105. Zhao Y, Fishman JA, Sergio JJ, Oliveros JL, Pearson DA, Szot GL, Wilkinson RA, Arn JS, Sachs DH, Sykes M. Immune restoration by fetal pig thymus grafts in T cell-depleted, thymectomized mice. J. Immunol. 1997;158:1641-1649.
100. Khan A, Sergio JJ, Zhao Y, Pearson DA, Sachs DH, Sykes M. Discordant xenogeneic neonatal thymic transplantation can induce donor-specific tolerance. Transplantation 1997;63:124-131.