MOHAMED SAYEGH

Summary

Affiliation: Harvard University
Country: USA

Publications

  1. pmc The programmed death-1 (PD-1) pathway regulates autoimmune diabetes in nonobese diabetic (NOD) mice
    Mohammed Javeed I Ansari
    Laboratory of Immunogenetics and Transplantation, Brigham and Women s Hospital, Boston, MA 02115, USA
    J Exp Med 198:63-9. 2003
  2. pmc A novel role of CD4 Th17 cells in mediating cardiac allograft rejection and vasculopathy
    Xueli Yuan
    Transplantation Research Center, Renal Division, Brigham and Women s Hospital and Children s Hospital Boston, Harvard Medical School, Boston, MA 02115, USA
    J Exp Med 205:3133-44. 2008
  3. ncbi request reprint Overview: future approaches to renal replacement and regeneration
    Mohamed H Sayegh
    Transplantation Research Center, Brigham and Women s Hospital and Children s Hospital Boston, Harvard Medical School, Boston, Massachusetts, USA
    J Am Soc Nephrol 15:1105. 2004
  4. pmc CD28-B7-mediated T cell costimulation in chronic cardiac allograft rejection: differential role of B7-1 in initiation versus progression of graft arteriosclerosis
    K S Kim
    Laboratory of Immunogenetics, Renal Division, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St, Boston, MA 02115, USA
    Am J Pathol 158:977-86. 2001
  5. pmc B7-dependent T-cell costimulation in mice lacking CD28 and CTLA4
    D A Mandelbrot
    Department of Pathology, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts, USA
    J Clin Invest 107:881-7. 2001
  6. ncbi request reprint Rejection of mouse cardiac allografts by costimulation in trans
    D A Mandelbrot
    Immunology Research Division, Department of Pathology, Brigham and Women s Hospital, Boston, MA 02115, USA
    J Immunol 167:1174-8. 2001
  7. ncbi request reprint CD28-independent costimulation of T cells in alloimmune responses
    A Yamada
    Laboratory of Immunogenetics and Transplantation and Immunology Research Division, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA
    J Immunol 167:140-6. 2001
  8. pmc The role of CD154-CD40 versus CD28-B7 costimulatory pathways in regulating allogeneic Th1 and Th2 responses in vivo
    K Kishimoto
    Laboratory of Immunogenetics and Transplantation, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    J Clin Invest 106:63-72. 2000
  9. pmc Costimulatory function and expression of CD40 ligand, CD80, and CD86 in vascularized murine cardiac allograft rejection
    W W Hancock
    Department of Pathology, New England Deaconess Hospital, Boston, MA 02215, USA
    Proc Natl Acad Sci U S A 93:13967-72. 1996
  10. pmc CD28-independent induction of experimental autoimmune encephalomyelitis
    T Chitnis
    Center for Neurologic Diseases, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, USA
    J Clin Invest 107:575-83. 2001

Research Grants

Detail Information

Publications96

  1. pmc The programmed death-1 (PD-1) pathway regulates autoimmune diabetes in nonobese diabetic (NOD) mice
    Mohammed Javeed I Ansari
    Laboratory of Immunogenetics and Transplantation, Brigham and Women s Hospital, Boston, MA 02115, USA
    J Exp Med 198:63-9. 2003
    ....
  2. pmc A novel role of CD4 Th17 cells in mediating cardiac allograft rejection and vasculopathy
    Xueli Yuan
    Transplantation Research Center, Renal Division, Brigham and Women s Hospital and Children s Hospital Boston, Harvard Medical School, Boston, MA 02115, USA
    J Exp Med 205:3133-44. 2008
    ..These results have important implications for the development of novel therapies to target this intractable problem in clinical solid organ transplantation...
  3. ncbi request reprint Overview: future approaches to renal replacement and regeneration
    Mohamed H Sayegh
    Transplantation Research Center, Brigham and Women s Hospital and Children s Hospital Boston, Harvard Medical School, Boston, Massachusetts, USA
    J Am Soc Nephrol 15:1105. 2004
  4. pmc CD28-B7-mediated T cell costimulation in chronic cardiac allograft rejection: differential role of B7-1 in initiation versus progression of graft arteriosclerosis
    K S Kim
    Laboratory of Immunogenetics, Renal Division, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St, Boston, MA 02115, USA
    Am J Pathol 158:977-86. 2001
    ..This study further defines functional differences between CD80 and CD86 costimulatory molecules in vivo...
  5. pmc B7-dependent T-cell costimulation in mice lacking CD28 and CTLA4
    D A Mandelbrot
    Department of Pathology, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts, USA
    J Clin Invest 107:881-7. 2001
    ..Finally, administration of CTLA4-Ig to CD28/CTLA4(-/-) cardiac allograft recipients significantly prolongs graft survival. These data support the existence of an additional receptor for B7 molecules that is neither CD28 nor CTLA4...
  6. ncbi request reprint Rejection of mouse cardiac allografts by costimulation in trans
    D A Mandelbrot
    Immunology Research Division, Department of Pathology, Brigham and Women s Hospital, Boston, MA 02115, USA
    J Immunol 167:1174-8. 2001
    ..This is the first demonstration that costimulation in trans can mediate an immune response in vivo and has important therapeutic implications...
  7. ncbi request reprint CD28-independent costimulation of T cells in alloimmune responses
    A Yamada
    Laboratory of Immunogenetics and Transplantation and Immunology Research Division, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA
    J Immunol 167:140-6. 2001
    ....
  8. pmc The role of CD154-CD40 versus CD28-B7 costimulatory pathways in regulating allogeneic Th1 and Th2 responses in vivo
    K Kishimoto
    Laboratory of Immunogenetics and Transplantation, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    J Clin Invest 106:63-72. 2000
    ....
  9. pmc Costimulatory function and expression of CD40 ligand, CD80, and CD86 in vascularized murine cardiac allograft rejection
    W W Hancock
    Department of Pathology, New England Deaconess Hospital, Boston, MA 02215, USA
    Proc Natl Acad Sci U S A 93:13967-72. 1996
    ..These data also suggest that long-term graft survival can be achieved without blockade of either T cell receptor-mediated signals or CD28-CD86 engagement...
  10. pmc CD28-independent induction of experimental autoimmune encephalomyelitis
    T Chitnis
    Center for Neurologic Diseases, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, USA
    J Clin Invest 107:575-83. 2001
    ..Our data show that EAE may develop in the absence of CD28 T-cell costimulation. These findings have implications for therapies aimed at blocking costimulatory signals in autoimmune diseases...
  11. ncbi request reprint Recipient MHC class II expression is required to achieve long-term survival of murine cardiac allografts after costimulatory blockade
    A Yamada
    Transplantation Unit, Surgical Services, Massachusetts General Hospital, Boston, MA 02114, USA
    J Immunol 167:5522-6. 2001
    ..These results suggest that an active CD4(+) response through the indirect pathway is necessary for costimulatory blockade to be effective in prolonging allograft survival...
  12. ncbi request reprint New insights in CD28-independent allograft rejection
    A Habicht
    Transplantation Research Center, Renal Division, Brigham and Women s Hospital and Children s Hospital Boston, Harvard Medical School, Boston, MA, USA
    Am J Transplant 7:1917-26. 2007
    ....
  13. ncbi request reprint Antibody-induced transplant arteriosclerosis is prevented by graft expression of anti-oxidant and anti-apoptotic genes
    W W Hancock
    Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
    Nat Med 4:1392-6. 1998
    ..These data show a role for protective genes in the prevention of chronic rejection, and indicate new approaches to protect grafts against development of transplant arteriosclerosis...
  14. ncbi request reprint The role of donor and recipient B7-1 (CD80) in allograft rejection
    X X Zheng
    Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
    J Immunol 159:1169-73. 1997
    ..These data also indicate that B7-1 and B7-2 are the only CD28 ligands relevant to cardiac allograft rejection in mice...
  15. ncbi request reprint Striking dichotomy of PD-L1 and PD-L2 pathways in regulating alloreactive CD4(+) and CD8(+) T cells in vivo
    A Habicht
    Transplantation Research Center, Brigham and Women s Hospital and the Children s Hospital of Boston, Boston, MA, USA
    Am J Transplant 7:2683-92. 2007
    ..We conclude that PD-L1 and PD-L2 function differently in regulating alloreactive T-cell activation in vivo, and PD-L2 is predominant in this model in limiting alloreactive CD8(+) T-cell proliferation...
  16. doi request reprint Regulatory T cells in transplantation: what we know and what we do not know
    M Y Yeung
    Transplantation Research Center, Renal Division, Brigham and Women s Hospital and Children s Hospital Boston and Harvard Medical School, Boston, Massachusetts, USA
    Transplant Proc 41:S21-6. 2009
    ..The impact of current immunosuppressive agents on Tregs will be reviewed, and future promising targets for Treg-based therapies will be explored...
  17. ncbi request reprint CTLA4Ig-induced linked regulation of allogeneic T cell responses
    R S Lee
    Transplantation Biology Research Center, Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA
    J Immunol 166:1572-82. 2001
    ..These data suggest that CTLA4Ig-induced inhibition of naive allogeneic T cell responses can be mediated through the generation of regulatory T cells via an IL-10-dependent mechanism...
  18. ncbi request reprint CTLA4-Ig: a novel immunosuppressive agent
    N Najafian
    Brigham and Women s Hospital, Renal Division, Immunogenetics and Transplantation, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA
    Expert Opin Investig Drugs 9:2147-57. 2000
    ....
  19. pmc Bacterial pathogens induce abscess formation by CD4(+) T-cell activation via the CD28-B7-2 costimulatory pathway
    A O Tzianabos
    Channing Laboratory, Department of Medicine, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    Infect Immun 68:6650-5. 2000
    ..These results demonstrate that abscess formation by pathogenic bacteria is under the control of a common effector mechanism that requires T-cell activation via the CD28-B7-2 pathway...
  20. pmc Cognate stimulatory B-cell-T-cell interactions are critical for T-cell help recruited by glycoconjugate vaccines
    H K Guttormsen
    Channing Laboratory, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA
    Infect Immun 67:6375-84. 1999
    ..Comparable results were obtained with pathway antagonists. These data suggest that MHC class II Ag-TCR, B7-CD28, and CD40-CD40L interactions are critical for immune responses to glycoconjugate vaccines in vivo...
  21. ncbi request reprint Interactions between cyclosporine and newer antidepressant medications
    J P Vella
    Laboratory of Immunogenetics and Transplantation, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    Am J Kidney Dis 31:320-3. 1998
    ..Intensive monitoring of the serum creatinine and cyclosporine level is indicated under such circumstances, with dose reductions performed as indicated...
  22. pmc Chronic cardiac rejection in the LEW to F344 rat model. Blockade of CD28-B7 costimulation by CTLA4Ig modulates T cell and macrophage activation and attenuates arteriosclerosis
    M E Russell
    Cardiovascular Biology Laboratory, Harvard School of Public Health, Boston, MA 02115, USA
    J Clin Invest 97:833-8. 1996
    ..Thus, T cell activation is a proximal event in the cascade that culminates in the arteriosclerosis of chronic rejection. Strategies for blocking T cell costimulation may help prevent chronic rejection in clinical transplantation...
  23. ncbi request reprint The antagonism of calcineurin inhibitors and costimulatory blockers: fact or fiction?
    A Izawa
    Laboratory of Immunogenetics and Transplantation, Brigham and Women s Hospital, and Division of Nephrology, Children s Hospital Boston, Harvard Medical School, Boston, MA 02115, USA
    Transplant Proc 36:570S-573S. 2004
    ..Here, we summarize the current understanding of the interaction between calcineurin inhibitors and T-cell costimulatory blockade strategies in transplantation...
  24. pmc Paradoxical functions of B7: CD28 costimulation in a MHC class II-mismatched cardiac transplant model
    J Yang
    Transplantation Research Center, Renal Division, Brigham and Women s Hospital, Children s Hospital Boston, Harvard Medical School, Boston, MA, USA
    Am J Transplant 9:2837-44. 2009
    ....
  25. ncbi request reprint P-glycoprotein--a novel therapeutic target for immunomodulation in clinical transplantation and autoimmunity?
    S Pendse
    Laboratory of Immunogenetics and Transplantation, Renal Division, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA
    Curr Drug Targets 4:469-76. 2003
    ....
  26. pmc Regulatory functions of self-restricted MHC class II allopeptide-specific Th2 clones in vivo
    A M Waaga
    Laboratory of Immunogenetics and Transplantation, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA
    J Clin Invest 107:909-16. 2001
    ..We suggest that self-restricted alloantigen-specific Th2 clones may regulate the alloimmune responses and promote long-term allograft survival and tolerance...
  27. pmc Indirect recognition of allopeptides promotes the development of cardiac allograft vasculopathy
    R S Lee
    The Transplantation Biology Research Center and Division of Cardiac Surgery, Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA
    Proc Natl Acad Sci U S A 98:3276-81. 2001
    ..001), but they also developed obstructive fibroproliferative coronary artery lesions much earlier than unimmunized controls (<9 vs. >30 days). These results definitively link indirect allorecognition and cardiac allograft vasculopathy...
  28. pmc Effect of targeted disruption of STAT4 and STAT6 on the induction of experimental autoimmune encephalomyelitis
    T Chitnis
    Center for Neurologic Diseases, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Clin Invest 108:739-47. 2001
    ..In addition, adoptive transfer studies confirm the regulatory functions of a Th2 environment in vivo. These novel data indicate that STAT4 and STAT6 genes play a critical role in regulating the autoimmune response in EAE...
  29. ncbi request reprint Specific MDR1 P-glycoprotein blockade inhibits human alloimmune T cell activation in vitro
    M H Frank
    Division of Nephrology, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA
    J Immunol 166:2451-9. 2001
    ..Our results define a novel role for P-gp in alloimmunity and thus raise the intriguing possibility that P-gp may represent a novel therapeutic target in allograft rejection...
  30. ncbi request reprint Membranous lupus nephritis in a renal allograft: response to mycophenolate mofetil therapy
    M D Denton
    Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Am J Transplant 1:288-92. 2001
    ..This is the first report of successful treatment of membranous lupus nephritis in an allograft using MMF. We review all cases of transplant-associated membranous lupus nephritis in the English literature...
  31. ncbi request reprint P-glycoprotein functions as a differentiation switch in antigen presenting cell maturation
    S S Pendse
    Transplantation Research Center, Children s Hospital Boston, Massachusetts, USA
    Am J Transplant 6:2884-93. 2006
    ..Our findings define a novel role for P-gp as a differentiation switch in APC maturation and resultant alloimmune Th1 responses, thereby identifying P-gp as a potential novel therapeutic target in allotransplantation...
  32. ncbi request reprint The evolution of the immunobiology of co-stimulatory pathways: clinical implications
    S Trikudanathan
    Transplantation Research Center, Renal Division, Brigham and Women s Hospital, Boston, MA 02115, USA
    Clin Exp Rheumatol 25:S12-21. 2007
    ....
  33. ncbi request reprint Indirect allorecognition of donor class I and II major histocompatibility complex peptides promotes the development of transplant vasculopathy
    K L Womer
    Laboratory of Immunogenetics and Transplantation, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Masachussets 02115, USA
    J Am Soc Nephrol 12:2500-6. 2001
    ..These novel observations provide definitive evidence of a link between indirect allorecognition and the development and progression of chronic rejection...
  34. ncbi request reprint Costimulation and autoimmune diabetes in BB rats
    B C Beaudette-Zlatanova
    Department of Medicine, The University of Massachusetts Medical School, Worcester, and Transplantation Research Center, Brigham and Women s Hospital, Boston, Massachusetts, USA
    Am J Transplant 6:894-902. 2006
    ....
  35. pmc Tolerance and chronic rejection
    K L Womer
    Laboratory of Immunogenetics and Transplantation, Renal Division, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA
    Philos Trans R Soc Lond B Biol Sci 356:727-38. 2001
    ..General mechanisms of CR and transplantation tolerance induction are discussed as well as the difficulties in translating small animals studies into large animals and humans...
  36. ncbi request reprint Accelerated memory cell homeostasis during T cell depletion and approaches to overcome it
    David C Neujahr
    Department of Medicine, University of Pennsylvania, Philadelphia 19104, USA
    J Immunol 176:4632-9. 2006
    ..These data have clinically relevant implications related to the development of novel strategies to overcome resistance to tolerance...
  37. ncbi request reprint Differential role of programmed death-ligand 1 [corrected] and programmed death-ligand 2 [corrected] in regulating the susceptibility and chronic progression of experimental autoimmune encephalomyelitis
    Bing Zhu
    Center for Neurologic Diseases, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    J Immunol 176:3480-9. 2006
    ..In conclusion, PD-L1 and PD-L2 differentially regulate the susceptibility and chronic progression of EAE in a strain-specific manner...
  38. ncbi request reprint Critical, but conditional, role of OX40 in memory T cell-mediated rejection
    Minh Diem Vu
    Transplant Research Center, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
    J Immunol 176:1394-401. 2006
    ..Our data demonstrate that memory T cells resisting to CD28/CD154 blockade in transplant rejection are sensitive to OX40 blockade and suggest that OX40 is a key therapeutic target in memory T cell-mediated rejection...
  39. ncbi request reprint Novel insights into the mechanism of action of FTY720 in a transgenic model of allograft rejection: implications for therapy of chronic rejection
    Antje Habicht
    Transplantation Research Center, Brigham and Women s Hospital and Children s Hospital, Boston, MA 02115, USA
    J Immunol 176:36-42. 2006
    ..These data have important implications for targeting the sphingosine 1-phosphate receptor 1 in solid organ transplantation...
  40. ncbi request reprint Combination treatment with donor-specific transfusions and cyclosporine a induces long-term survival of cardiac allografts in miniature Swine
    Ruediger Hoerbelt
    Transplantation Biology Research Center, Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
    Transplantation 80:1275-82. 2005
    ..To evaluate whether pretransplant donor-specific transfusions (DST) can induce tolerance to cardiac allografts in large animals, heterotopic cardiac transplants were performed across a class I MHC barrier in inbred miniature swine...
  41. pmc Requirements for induction and maintenance of peripheral tolerance in stringent allograft models
    Masayuki Sho
    Transplantation Research Center, Brigham and Women s Hospital and Children s Hospital Boston, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 102:13230-5. 2005
    ..These results provide insight into the mechanisms of tolerance in stringent models and provide a rational basis for innovative tolerogenic strategies in humans...
  42. ncbi request reprint Analysis of the role of negative T cell costimulatory pathways in CD4 and CD8 T cell-mediated alloimmune responses in vivo
    Toshiro Ito
    Transplantation Research Center, Brigham and Women s Hospital and Children s Hospital Boston, MA 02115, USA
    J Immunol 174:6648-56. 2005
    ..Harnessing physiological mechanisms that regulate alloimmunity should lead to development of novel strategies to induce durable and reproducible transplantation tolerance...
  43. pmc Requirement of homotypic NK-cell interactions through 2B4(CD244)/CD48 in the generation of NK effector functions
    Kyung Mi Lee
    Department of Pathology, University of Chicago, IL, USA
    Blood 107:3181-8. 2006
    ..Thus, these data identify a novel mechanism whereby NK effector function is regulated via homotypic 2B4/CD48 interactions...
  44. ncbi request reprint ABCB5-mediated doxorubicin transport and chemoresistance in human malignant melanoma
    Natasha Y Frank
    Department of Genetics, Children s Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115, USA
    Cancer Res 65:4320-33. 2005
    ....
  45. pmc Insulin-induced remission in new-onset NOD mice is maintained by the PD-1-PD-L1 pathway
    Brian T Fife
    UCSF Diabetes Center, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, and Transplantation Research Center, Brigham and Women s Hospital, Boston, MA 02115, USA
    J Exp Med 203:2737-47. 2006
    ....
  46. ncbi request reprint Characterization of donor dendritic cells and enhancement of dendritic cell efflux with CC-chemokine ligand 21: a novel strategy to prolong islet allograft survival
    Paolo Fiorina
    Transplantation Research Center TRC, Children s Hospital and Brigham and Women s Hospital, Harvard Medical School, 221 Longwood Ave, Boston, MA 02115, USA
    Diabetes 56:912-20. 2007
    ..This study introduces dDCs and rDCs as two distinct types of DCs and provides novel data with clinical implications to use chemokine-based DC-depleting strategies to prolong islet allograft survival...
  47. doi request reprint Phenotypic and functional differences between wild-type and CCR2-/- dendritic cells: implications for islet transplantation
    Paolo Fiorina
    Transplantation Research Center, Children s Hospital and Brigham and Women s Hospital, Harvard Medical School, Boston, MA, USA
    Transplantation 85:1030-8. 2008
    ..Here, we provide evidence that lack of CCR2 could lead to the generation of functionally and phenotypically different DC, which in part could explain the benefits observed in transplanting islets in CCR2 recipients...
  48. pmc Induction of transplantation tolerance by combining non-myeloablative conditioning with delivery of alloantigen by T cells
    Chaorui Tian
    Transplantation Research Center, Brigham and Women s Hospital and Children s Hospital Boston, Harvard Medical School, 221 Longwood Avenue LM303, Boston, MA 02115, USA
    Clin Immunol 127:130-7. 2008
    ..These data suggest robust tolerance can be established without the need for bone marrow transplantation using clinically relevant non-myeloablative conditioning combined with antigen delivery by T cells...
  49. doi request reprint Regulating rejection with cell therapy
    Mohamed H Sayegh
    Nat Biotechnol 26:191-2. 2008
  50. doi request reprint Critical role of donor tissue expression of programmed death ligand-1 in regulating cardiac allograft rejection and vasculopathy
    Jun Yang
    Transplantation Research Center, Brigham and Women s Hospital, Harvard Medical School, 221 Longwood Ave, Boston, MA 02115, USA
    Circulation 117:660-9. 2008
    ..We investigated the role of recipient versus donor PD-1 ligands in the pathogenesis of allograft rejection with emphasis on the role of tissue expression in regulating this alloimmune response in vivo...
  51. pmc The emerging role of T cell Ig mucin 1 in alloimmune responses in an experimental mouse transplant model
    Takuya Ueno
    Transplantation Research Center, Renal Division, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, USA
    J Clin Invest 118:742-51. 2008
    ..These studies define previously unknown functions of TIM-1 in regulating alloimmune responses in vivo and may provide a novel approach to promoting transplantation tolerance...
  52. ncbi request reprint Induction of robust diabetes resistance and prevention of recurrent type 1 diabetes following islet transplantation by gene therapy
    Chaorui Tian
    Transplantation Research Center, Renal Division, Brigham and Women s Hospital, Children s Hospital Boston, Harvard Medical School, Boston, MA 02115, USA
    J Immunol 179:6762-9. 2007
    ....
  53. pmc Proinflammatory functions of vascular endothelial growth factor in alloimmunity
    Marlies E J Reinders
    Division of Nephrology, Department of Medicine, Children s Hospital, 300 Longwood Avenue, Boston, Massachusetts 02115, USA
    J Clin Invest 112:1655-65. 2003
    ..Thus, VEGF appears to be functional in acute allograft rejection via its effects on leukocyte trafficking. Together, these observations provide mechanistic insight into the proinflammatory function of VEGF in immunity...
  54. ncbi request reprint A link between PDL1 and T regulatory cells in fetomaternal tolerance
    Antje Habicht
    Transplantation Research Center, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    J Immunol 179:5211-9. 2007
    ..This is the first report providing evidence for a link between PDL1 and T regulatory cells in mediating fetomaternal tolerance...
  55. pmc PDL1 is required for peripheral transplantation tolerance and protection from chronic allograft rejection
    Katsunori Tanaka
    Transplantation Research Center, Renal Division, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    J Immunol 179:5204-10. 2007
    ..Expression of PDL1 in donor tissue is critical for prevention of in situ graft pathology and chronic rejection...
  56. ncbi request reprint Role of ICOS pathway in autoimmune and alloimmune responses in NOD mice
    Mohammed Javeed I Ansari
    Transplantation Research Center, Renal Division, Brigham and Women s Hospital and Children s Hospital Boston, Harvard Medical School, Boston, MA 02115, USA
    Clin Immunol 126:140-7. 2008
    ..We conclude that in islet transplantation and autoimmune diabetes, ICOS blockade can be effective in inhibiting alloimmunity and preventing autoimmunity but is ineffective in inhibiting recurrence of autoimmunity...
  57. pmc Tissue expression of PD-L1 mediates peripheral T cell tolerance
    Mary E Keir
    Department of Pathology, Brigham and Women s Hospital and Children s Hospital Boston, MA 02115, USA
    J Exp Med 203:883-95. 2006
    ..These data provide evidence that PD-L1 expression on parenchymal cells rather than hematopoietic cells protects against autoimmune diabetes and point to a novel role for PD-1-PD-L1 interactions in mediating tissue tolerance...
  58. ncbi request reprint A novel alloantigen-specific CD8+PD1+ regulatory T cell induced by ICOS-B7h blockade in vivo
    Atsushi Izawa
    Transplantation Research Center, Renal Division, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    J Immunol 179:786-96. 2007
    ..These results describe a novel allospecific regulatory CD8(+)PD1(+) T cell induced by ICOS-B7h blockade in vivo...
  59. pmc Differential engagement of Tim-1 during activation can positively or negatively costimulate T cell expansion and effector function
    Sheng Xiao
    Center for Neurologic Diseases, Brigham and Women s Hospital and Children s Hospital Boston, Harvard Medical School, Boston, MA 02115, USA
    J Exp Med 204:1691-702. 2007
    ..These data indicate that Tim-1 regulates T cell responses and that Tim-1 engagement can alter T cell function depending on the affinity/avidity with which it is engaged...
  60. ncbi request reprint Mechanisms of PDL1-mediated regulation of autoimmune diabetes
    Indira Guleria
    Transplantation Research Center, Brigham and Women s Hospital and Children s Hospital Boston, Harvard Medical School, Boston, MA 02115, USA
    Clin Immunol 125:16-25. 2007
    ..These data provide strong evidence that PDL1 regulates autoimmune diabetes by limiting the expansion of CD4+ and CD8+ autoreactive T cells, and define the timing and locale of PDL1-mediated regulation of type 1 diabetes...
  61. pmc Mechanisms underlying blockade of allograft acceptance by TLR ligands
    Paige M Porrett
    Department of Surgery, University of Pennsylvania, Philadelphia, PA 19104, USA
    J Immunol 181:1692-9. 2008
    ..Instead, graft destruction results from the ability of CpG to drive Th1 differentiation and interfere with immunoregulation established by alloreactive natural CD4(+)Foxp3(+) Tregs...
  62. ncbi request reprint Role of the ICOS-B7h costimulatory pathway in the pathophysiology of chronic allograft rejection
    Hisanori Kashizuka
    Department of Surgery, Nara Medical University School of Medicine, Kashihara, Nara, Japan
    Transplantation 79:1045-50. 2005
    ..Recent studies indicated that the ICOS-B7h pathway plays an important role in alloimmune responses. We further investigated the role of the ICOS pathway in the pathologic process of chronic rejection in vivo...
  63. ncbi request reprint Activation of alloreactive CD8+ T cells operates via CD4-dependent and CD4-independent mechanisms and is CD154 blockade sensitive
    Yuan Zhai
    Dumont University of California, Los Angeles, Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, School of Medicine, 90095, USA
    J Immunol 170:3024-8. 2003
    ..Indeed, CD154 blockade was effective in preventing CD8(+) T cell-mediated cardiac allograft rejection...
  64. ncbi request reprint The role of the CD134-CD134 ligand costimulatory pathway in alloimmune responses in vivo
    Xueli Yuan
    Laboratory of Immunogenetics and Transplantation, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    J Immunol 170:2949-55. 2003
    ..Understanding the mechanisms of collaboration between these different pathways is important for the development of novel strategies to promote long-term allograft survival...
  65. ncbi request reprint CD4+ T cells mediate abscess formation in intra-abdominal sepsis by an IL-17-dependent mechanism
    Doo Ryeon Chung
    Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    J Immunol 170:1958-63. 2003
    ..These data delineate the specific T cell response necessary for the development of intra-abdominal abscesses and underscore the role of IL-17 in this disease process...
  66. pmc New insights into the interactions between T-cell costimulatory blockade and conventional immunosuppressive drugs
    Masayuki Sho
    Laboratory of Immunogenetics and Transplantation, Brigham and Women s Hospital, Boston, Massachusetts, USA
    Ann Surg 236:667-75. 2002
    ..To determine the precise in vivo interaction between T-cell costimulatory blockade and conventional immunosuppression in transplantation...
  67. ncbi request reprint The role of autoimmunity in islet allograft destruction: major histocompatibility complex class II matching is necessary for autoimmune destruction of allogeneic islet transplants after T-cell costimulatory blockade
    Leila Makhlouf
    Laboratory of Immunogenetics and Transplantation, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    Diabetes 51:3202-10. 2002
    ..Our results may have implications for the design of future clinical trials in islet transplantation...
  68. ncbi request reprint T-cell response to cardiac myosin persists in the absence of an alloimmune response in recipients with chronic cardiac allograft rejection
    Hillary K Rolls
    Schepens Eye Research Institute and Department of Ophthalmology, Harvard Medical School, Boston, MA 02114 2500, USA
    Transplantation 74:1053-7. 2002
    ..This response contributes to transplant rejection in that its modulation affects cardiac graft survival. This study investigates whether anti-CM T cells undergo activation and expansion in mice with chronic cardiac allograft rejection...
  69. ncbi request reprint The relative contribution of direct and indirect antigen recognition pathways to the alloresponse and graft rejection depends upon the nature of the transplant
    Ben M Illigens
    Cellular and Molecular Immunology Laboratory, Schepens Eye Research Institute and Department of Ophthalmology, Harvard Medical School, 20 Staniford Street, Boston, MA 02114, USA
    Hum Immunol 63:912-25. 2002
    ..The implications of this finding for understanding the cellular mechanisms by which rejection is mediated in different transplant models are discussed...
  70. ncbi request reprint Physiological mechanisms of regulating alloimmunity: cytokines, CTLA-4, CD25+ cells, and the alloreactive T cell clone size
    Masayuki Sho
    Department of Medicine, Children s Hospital, Laboratory of Immunogenetics and Transplantation, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    J Immunol 169:3744-51. 2002
    ..These data demonstrate that cytokine regulation, CTLA-4 negative signaling, and T cell apoptosis play critical roles in regulating alloimmunity, especially under conditions where the alloreactive T cell clone size is relatively small...
  71. ncbi request reprint The role of CC chemokine receptor 5 (CCR5) in islet allograft rejection
    Reza Abdi
    Laboratory of Immunogenetics and Transplantation, Renal Division, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    Diabetes 51:2489-95. 2002
    ..Targeting this chemokine receptor, therefore, may provide a clinically useful strategy to prevent islet allograft rejection...
  72. ncbi request reprint Modulation of tissue-specific immune response to cardiac myosin can prolong survival of allogeneic heart transplants
    Eugenia V Fedoseyeva
    Cellular and Molecular Immunology Laboratory, Schepens Eye Research Institute and Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA
    J Immunol 169:1168-74. 2002
    ....
  73. ncbi request reprint A novel CD154 monoclonal antibody in acute and chronic rat vascularized cardiac allograft rejection
    Xueli Yuan
    Laboratory of Immunogenetics and Transplantation, Brigham and Women s Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, U S A
    Transplantation 73:1736-42. 2002
    ..However, the role of the CD40-CD154 pathway in the development of chronic rejection and the effects of CD154 targeting on progression of chronic rejection have not been evaluated...
  74. pmc Th1 cytokines, programmed cell death, and alloreactive T cell clone size in transplant tolerance
    Koji Kishimoto
    Laboratory of Immunogenetics and Transplantation, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Clin Invest 109:1471-9. 2002
    ..These data have implications for the design of tolerance strategies in transplant recipients with varying degrees of MHC mismatching...
  75. pmc CD4+ T cells regulate surgical and postinfectious adhesion formation
    Doo Ryeon Chung
    Channing Laboratory, Department of Medicine, 181 Longwood Avenue, Boston, MA 02115, USA
    J Exp Med 195:1471-8. 2002
    ....
  76. ncbi request reprint Mechanisms of targeting CD28 by a signaling monoclonal antibody in acute and chronic allograft rejection
    Victor M Dong
    Laboratory of Immunogenetics and Transplantation, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    Transplantation 73:1310-7. 2002
    ..Finally, we report on the potential mechanisms of action of targeting CD28 in vivo...
  77. ncbi request reprint Anti-CD28 monoclonal antibody therapy prevents chronic rejection of renal allografts in rats
    Igor A Laskowski
    Surgical Research Laboratory, Harvard Medical School Cambridge, Massachusetts, USA
    J Am Soc Nephrol 13:519-27. 2002
    ..These data support an important role for T cell costimulation in the evolution of the chronic process...
  78. ncbi request reprint Interaction between ICOS-B7RP1 and B7-CD28 costimulatory pathways in alloimmune responses in vivo
    Alan D Salama
    Laboratory of Immunogenetics and Transplantation, Brigham and Women s Hospital, Harvard Medical School, Boston, MA, USA
    Am J Transplant 3:390-5. 2003
    ..2 expression following early B7RP1 blockade. This is the first report describing the complex interactions between ICOS-B7RP1 and B7-CD28 costimulatory pathways in alloimmunity in vivo...
  79. ncbi request reprint CD45RB-targeting strategies for promoting long-term allograft survival and preventingchronic allograft vasculopathy
    Masayuki Sho
    Department of Medicine, Children s Hospital, Brigham and Women s Hospital, Harvard Medical School, Boston, MA, USA
    Transplantation 75:1142-6. 2003
    ..We evaluated the in vivo effect of anti-CD45RB monoclonal antibody (mAb) treatment in combination with conventional immunosuppression or costimulatory blockade strategies as a therapeutic modality for future clinical application...
  80. ncbi request reprint Alloreactive T cell responses and acute rejection of single class II MHC-disparate heart allografts are under strict regulation by CD4+ CD25+ T cells
    Soren Schenk
    Department of Biomedical Engineering, Cleveland Clinic Foundation, Cleveland, OH 44195, USA
    J Immunol 174:3741-8. 2005
    ..H-2bm12 heart allografts by C57BL/6 recipients is inhibited by the emergence of CD25+ regulatory cells that restrict the clonal expansion of alloreactive T cells...
  81. ncbi request reprint Role of the programmed death-1 pathway in regulation of alloimmune responses in vivo
    Sigrid E Sandner
    Transplantation Research Center, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    J Immunol 174:3408-15. 2005
    ..These data demonstrate a critical role for the PD-1 pathway, particularly PD-1/PD-L1 interactions, in the regulation of alloimmune responses in vivo...
  82. ncbi request reprint CD70 signaling is critical for CD28-independent CD8+ T cell-mediated alloimmune responses in vivo
    Akira Yamada
    Transplantation Research Center, Brigham and Women s Hospital and Children s Hospital Boston, Harvard Medical School, Boston, MA 02115, USA
    J Immunol 174:1357-64. 2005
    ..These novel findings have important implications for the development of transplantation tolerance-inducing strategies in primates and humans, in which CD8(+) T cell depletion is currently mandatory...
  83. ncbi request reprint Mechanisms of tolerance induced by donor-specific transfusion and ICOS-B7h blockade in a model of CD4+ T-cell-mediated allograft rejection
    Sigrid E Sandner
    Transplantation Research Center, Brigham and Women s Hospital, Harvard Medical School, Boston, MA, USA
    Am J Transplant 5:31-9. 2005
    ....
  84. ncbi request reprint Transplantation tolerance. A complex scenario awaiting clinical applicability
    Mohamed H Sayegh
    Transplantation Research Center, Brigham and Women s Hospital and Children s Hospital Boston, Harvard Medical School, Boston, Mass, USA
    Contrib Nephrol 146:95-104. 2005
    ..immunetolerance.org). In this review we will highlight the promise and challenges of making transplantation tolerance a clinical reality...
  85. ncbi request reprint Alloreactivity in renal transplant recipients with and without chronic allograft nephropathy
    Emilio D Poggio
    Department of Immunology, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    J Am Soc Nephrol 15:1952-60. 2004
    ..Immune monitoring to predict long-term outcome should include multiple measures of cellular and humoral immunity...
  86. ncbi request reprint Different costimulatory and growth factor requirements for CD4+ and CD8+ T cell-mediated rejection
    Minh Diem Vu
    Department of Medicine, Harvard Medical School, Boston, MA 02215, USA
    J Immunol 173:214-21. 2004
    ..We conclude that CD4(+) and CD8(+) T cells exhibit distinct sensitivity to growth factor blockade in transplant rejection, and CD28/CD154-independent rejection is sensitive to rapamycin and appears to be supported by OX40 costimulation...
  87. pmc Neural stem/progenitor cells express costimulatory molecules that are differentially regulated by inflammatory and apoptotic stimuli
    Jaime Imitola
    Center for Neurologic Diseases, Brigham and Women s Hospital, Harvard Medical School, Boston, USA
    Am J Pathol 164:1615-25. 2004
    ....
  88. ncbi request reprint Defining Th1 and Th2 immune responses in a reciprocal cytokine environment in vivo
    Tanuja Chitnis
    Center for Neurologic Diseases, Laboratory of Immunogenetics and Transplantation, Brigham and Women s Hospital, Harvard School of Public Health, Harvard Medical School, Boston, MA 02115, USA
    J Immunol 172:4260-5. 2004
    ..These data have implications for the treatment of immune-mediated diseases by immunomodulatory agents that alter the cytokine milieu in vivo...
  89. ncbi request reprint Critical role of OX40 in CD28 and CD154-independent rejection
    Gulcin Demirci
    Department of Medicine, Harvard Medical School, and Division of Immunology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
    J Immunol 172:1691-8. 2004
    ..Our study revealed a key cellular mechanism of rejection and identified OX40 as a critical alternative costimulatory molecule in CD28/CD154-independent rejection...
  90. ncbi request reprint Cutting edge: transplantation tolerance through enhanced CTLA-4 expression
    Charlotte Ariyan
    Department of Surgery, Yale Medical School, New Haven, CT 06520, USA
    J Immunol 171:5673-7. 2003
    ..These data demonstrate a specific role for CTLA-4 in anti-CD45RB-mediated tolerance and indicate that CTLA-4 up-regulation can directly promote allograft survival...
  91. ncbi request reprint New TCR transgenic model for tracking allospecific CD4 T-cell activation and tolerance in vivo
    Sigrid E Sandner
    Division of Nephrology, The Children s Hospital, Harvard Medical School, Boston, MA, USA
    Am J Transplant 3:1242-50. 2003
    ..We describe the first model for tracking alloreactive CD4+ T-cell activation in vivo. It provides a powerful tool for studying CD4+ T-cell mediated alloimmune responses and mechanisms of tolerance induction in vivo...
  92. ncbi request reprint Allorecognition and effector pathways of islet allograft rejection in normal versus nonobese diabetic mice
    Leila Makhlouf
    Laboratory of Immunogenetics and Transplantation, Renal Division, Department of Medicine, Brigham and Women s Hospital, Boston, Massachusetts, USA
    J Am Soc Nephrol 14:2168-75. 2003
    ..These data shed light on the mechanisms of islet allograft rejection in different responder strains, including those with autoimmunity...
  93. pmc The role of the ICOS-B7h T cell costimulatory pathway in transplantation immunity
    Hiroshi Harada
    Department of Medicine, Children s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    J Clin Invest 112:234-43. 2003
    ..These data define the complex functions of the ICOS-B7h pathway in regulating alloimmune responses in vivo...
  94. pmc Critical role of the programmed death-1 (PD-1) pathway in regulation of experimental autoimmune encephalomyelitis
    Alan D Salama
    Laboratory of Immunogenetics and Transplantation, Children s Hospital, Harvard Medical School, Boston, MA 02115, USA
    J Exp Med 198:71-8. 2003
    ..Interestingly, PD-L2 but not PD-L1 blockade in WT animals also resulted in disease augmentation. Our data are the first demonstration that the PD-1 pathway plays a critical role in regulating EAE...
  95. ncbi request reprint Enzyme-linked immunosorbent spot assay analysis of peripheral blood lymphocyte reactivity to donor HLA-DR peptides: potential novel assay for prediction of outcomes for renal transplant recipients
    Nader Najafian
    Laboratory of Immunogenetics and Transplantation, Brigham and Women s Hospital, Nephrology Division, Children s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Am Soc Nephrol 13:252-9. 2002
    ....

Research Grants2

  1. INTRATHYMIC TRANSPLANTATION TOLERANCE BY MHC PEPTIDES
    MOHAMED SAYEGH; Fiscal Year: 2003
    ..Results from these studies should yield clinically relevant information facilitating development of novel strategies to induce donor-specific tolerance. ..
  2. Immunopathogenesis of Chronic Allograft Rejection
    MOHAMED SAYEGH; Fiscal Year: 2005
    ..abstract_text> ..