Megan Sykes

Summary

Affiliation: Harvard University
Country: USA

Publications

  1. ncbi Treatment of severe autoimmune disease by stem-cell transplantation
    Megan Sykes
    Bone Marrow Transplantation Section, Transplantation Biology Research Center, Massachusetts General Hospital Harvard Medical School, MGH East, Building 149 5102, 13th Street, Boston, Massachusetts 02129, USA
    Nature 435:620-7. 2005
  2. ncbi Distinct requirements for achievement of allotolerance versus reversal of autoimmunity via nonmyeloablative mixed chimerism induction in NOD mice
    Boris Nikolic
    Nephrology Division, Massachusetts General Hospital Harvard Medical School, Boston, MA, USA
    Transplantation 89:23-32. 2010
  3. ncbi Rapid deletional peripheral CD8 T cell tolerance induced by allogeneic bone marrow: role of donor class II MHC and B cells
    Thomas Fehr
    Transplantation Biology Research Center, Massachusetts General Hospital Harvard Medical School, Boston, MA 02129, USA
    J Immunol 181:4371-80. 2008
  4. ncbi 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
    Thomas Fehr
    Bone Marrow Transplantation Section, Transplantation Biology Research Center, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02129, USA
    Eur J Immunol 35:2679-90. 2005
  5. ncbi A CD8 T cell-intrinsic role for the calcineurin-NFAT pathway for tolerance induction in vivo
    Thomas Fehr
    Transplantation Biology Research Center, Massachusetts General Hospital Harvard Medical School, Boston, MA, USA
    Blood 115:1280-7. 2010
  6. ncbi Mechanisms of the antitumor 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-deriv
    Marie-Therese Rubio
    Transplantation Biology Research Center, Bone Marrow Transplantation Section, Massachusetts General Hospital, Harvard Medical School, 13th Street, Boston, MA 02129, USA
    J Immunol 175:665-76. 2005
  7. ncbi HLA-mismatched renal transplantation without maintenance immunosuppression
    Tatsuo Kawai
    Transplantation Unit, Massachusetts General Hospital, and Harvard Medical School, Boston, USA
    N Engl J Med 358:353-61. 2008
  8. ncbi GalT-KO pigs: is the cup half empty or half full?
    David H Sachs
    Transplantation Biology Research Center, Massachusetts General Hospital, Charlestown, MA, USA
    Transplantation 84:12-4. 2007
  9. ncbi Xenogeneic thymokidney and thymic tissue transplantation in a pig-to-baboon model: I. Evidence for pig-specific T-cell unresponsiveness
    Rolf N Barth
    Transplantation Biology Research Center, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA
    Transplantation 75:1615-24. 2003
  10. ncbi Comparison of human T cell repertoire generated in xenogeneic porcine and human thymus grafts
    Ichiro Shimizu
    Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
    Transplantation 86:601-10. 2008

Detail Information

Publications98

  1. ncbi Treatment of severe autoimmune disease by stem-cell transplantation
    Megan Sykes
    Bone Marrow Transplantation Section, Transplantation Biology Research Center, Massachusetts General Hospital Harvard Medical School, MGH East, Building 149 5102, 13th Street, Boston, Massachusetts 02129, USA
    Nature 435:620-7. 2005
    ..The outcome of ongoing clinical trials, as well as of studies in patients and animal models, will help to determine the role that stem-cell transplantation can play in the treatment of autoimmune diseases...
  2. ncbi Distinct requirements for achievement of allotolerance versus reversal of autoimmunity via nonmyeloablative mixed chimerism induction in NOD mice
    Boris Nikolic
    Nephrology Division, Massachusetts General Hospital Harvard Medical School, Boston, MA, USA
    Transplantation 89:23-32. 2010
    ..We developed low intensity regimens for the induction of mixed chimerism and examined the effects on autoimmunity in prediabetic nonobese diabetic (NOD) mice...
  3. ncbi Rapid deletional peripheral CD8 T cell tolerance induced by allogeneic bone marrow: role of donor class II MHC and B cells
    Thomas Fehr
    Transplantation Biology Research Center, Massachusetts General Hospital Harvard Medical School, Boston, MA 02129, USA
    J Immunol 181:4371-80. 2008
    ..Thus, BM-derived B cells are potent tolerogenic APCs for alloreactive CD8 cells...
  4. ncbi 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
    Thomas Fehr
    Bone Marrow Transplantation Section, Transplantation Biology Research Center, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02129, USA
    Eur J Immunol 35:2679-90. 2005
    ..Thus, a novel, rapid form of regulation by CD4+CD25- T cells permits initial CD8 T cell tolerance in this model. Rapid peripheral deletion of donor-specific CD8 T cells precludes an ongoing requirement for CD4 T cell-mediated regulation...
  5. ncbi A CD8 T cell-intrinsic role for the calcineurin-NFAT pathway for tolerance induction in vivo
    Thomas Fehr
    Transplantation Biology Research Center, Massachusetts General Hospital Harvard Medical School, Boston, MA, USA
    Blood 115:1280-7. 2010
    ..Thus, our study reveals a CD8 T cell-intrinsic NFAT1 requirement for CD8 tolerance in vivo...
  6. ncbi Mechanisms of the antitumor 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-deriv
    Marie-Therese Rubio
    Transplantation Biology Research Center, Bone Marrow Transplantation Section, Massachusetts General Hospital, Harvard Medical School, 13th Street, Boston, MA 02129, USA
    J Immunol 175:665-76. 2005
    ..The pathways of donor marrow and tumor rejection lead to the development of tumor-specific cell-mediated cytotoxic responses that are not due to bystander killing by alloreactive T cells...
  7. ncbi HLA-mismatched renal transplantation without maintenance immunosuppression
    Tatsuo Kawai
    Transplantation Unit, Massachusetts General Hospital, and Harvard Medical School, Boston, USA
    N Engl J Med 358:353-61. 2008
    ....
  8. ncbi GalT-KO pigs: is the cup half empty or half full?
    David H Sachs
    Transplantation Biology Research Center, Massachusetts General Hospital, Charlestown, MA, USA
    Transplantation 84:12-4. 2007
  9. ncbi Xenogeneic thymokidney and thymic tissue transplantation in a pig-to-baboon model: I. Evidence for pig-specific T-cell unresponsiveness
    Rolf N Barth
    Transplantation Biology Research Center, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA
    Transplantation 75:1615-24. 2003
    ..Further strategies to address humoral rejection could prolong graft survival and result in long-term tolerance to xenografts...
  10. ncbi Comparison of human T cell repertoire generated in xenogeneic porcine and human thymus grafts
    Ichiro Shimizu
    Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
    Transplantation 86:601-10. 2008
    ..In this study, we assessed the diversity of the human T cell repertoire generated in porcine thymic xenografts. We also examined the ability of porcine thymus grafts to coexist with human thymus grafts...
  11. ncbi Paradoxical effects of IFN-gamma in graft-versus-host disease reflect promotion of lymphohematopoietic graft-versus-host reactions and inhibition of epithelial tissue injury
    Hui Wang
    Bone Marrow Transplantation Section, Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical, Boston, MA 02129, USA
    Blood 113:3612-9. 2009
    ..Furthermore, the magnitude of GVL is correlated with the strength of LGVHR, and IFN-gamma reduces the potential of this alloreactivity to cause epithelial tissue GVHD...
  12. ncbi Vascularized thymic lobe transplantation in a pig-to-baboon model: a novel strategy for xenogeneic tolerance induction and T-cell reconstitution
    Shin Yamamoto
    Transplantation Biology Research Center, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02129, USA
    Transplantation 80:1783-90. 2005
    ..When coupled with additional strategies aimed at silencing humoral rejection, VTL transplantation may significantly prolong xenograft survival and result in long-term tolerance...
  13. ncbi Mechanisms of early peripheral CD4 T-cell tolerance induction by anti-CD154 monoclonal antibody and allogeneic bone marrow transplantation: evidence for anergy and deletion but not regulatory cells
    Josef Kurtz
    Bone Marrow Transplantation Section, Transplantation Biology Research Center, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02129, USA
    Blood 103:4336-43. 2004
    ....
  14. ncbi Peripheral deletional tolerance of alloreactive CD8 but not CD4 T cells is dependent on the PD-1/PD-L1 pathway
    Fabienne Haspot
    Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA
    Blood 112:2149-55. 2008
    ..These studies demonstrate a dichotomy between the requirements for CD4 and CD8 tolerance and identify a role for PD-1 in the rapid tolerization of an alloreactive T-cell population via a deletional mechanism...
  15. ncbi Host MHC class II+ antigen-presenting cells and CD4 cells are required for CD8-mediated graft-versus-leukemia responses following delayed donor leukocyte infusions
    Ronjon Chakraverty
    Transplantation Biology Research Center, Bone Marrow Transplantation Section, Massachusetts General Hospital/Harvard Medical School, MGH-East, 13th Street, Boston, MA 02129, USA
    Blood 108:2106-13. 2006
    ....
  16. ncbi Invariant NKT cells are required for antitumor responses induced by host-versus-graft responses
    Toshiki I Saito
    Bone Marrow Transplantation Section, Transplantation Biology Research Center, Massachusetts General Hospital Harvard Medical School, Boston, MA 02129, USA
    J Immunol 185:2099-105. 2010
    ..Our studies demonstrate a central role for iNKTs in promoting RLI-induced anti-tumor effects and suggest that this pathway involved promotion of the activation of recipient NK cells and DCs...
  17. ncbi Monitoring antidonor alloantibodies as a predictive assay for renal allograft tolerance/long-term observations in nonhuman primates
    Svjetlan Boskovic
    Department of Surgery, Transplantation Unit, Harvard Medical School at Massachusetts General Hospital, Boston, MA 02114, USA
    Transplantation 82:819-25. 2006
    ....
  18. ncbi T cells from presensitized donors fail to cause graft-versus-host disease in a pig-to-mouse xenotransplantation model
    Hiroshi Eguchi
    Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, 13th Street, Boston, MA 02129, USA
    Transplantation 78:1609-17. 2004
    ..CONCLUSION: These results demonstrate that porcine T-cell function is severely impaired in the xenogeneic murine microenvironment...
  19. ncbi Roles of deletion and regulation in creating mixed chimerism and allograft tolerance using a nonlymphoablative irradiation-free protocol
    Christoph Domenig
    Transplantation Research Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
    J Immunol 175:51-60. 2005
    ..In this model, both deletional and immunoregulatory mechanisms are active during the induction and/or maintenance of allograft tolerance through creation of MC using a potentially clinically applicable regimen...
  20. ncbi An essential role for IFN-gamma in regulation of alloreactive CD8 T cells following allogeneic hematopoietic cell transplantation
    Wannee Asavaroengchai
    Bone Marrow Transplantation Section, Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02129, USA
    Biol Blood Marrow Transplant 13:46-55. 2007
    ..These data show that IFN-gamma negatively regulates the CD8 T cell response by inhibiting cell division and promoting cell death and suggest that blockade of IFN-gamma could augment the severity of GVHD in patients undergoing allo-HCT...
  21. ncbi Graft-versus-host-reactive donor CD4 cells can induce T cell-mediated rejection of the donor marrow in mixed allogeneic chimeras prepared with nonmyeloablative conditioning
    Yong-Mi Kim
    Transplantation Biology Research Center, Bone Marrow Transplantation Section, Massachusetts General Hospital/Harvard Medical School, MGH-East Bldg 149-5102, 13th St, Boston, MA 02129, USA
    Blood 103:732-9. 2004
    ..Thus, DLIs can paradoxically induce marrow rejection by residual host alphabeta T cells. These results have implications for the timing of and use of subset depletion of DLIs in recipients of nonmyeloablative transplants...
  22. ncbi Earlier low-dose TBI or DST overcomes CD8+ T-cell-mediated alloresistance to allogeneic marrow in recipients of anti-CD40L
    Yasuo Takeuchi
    Bone Marrow Transplantation Section, Transplantation Biology Research Center, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA
    Am J Transplant 4:31-40. 2004
    ..These nontoxic regimens overcome CD8+ and CD4+ T-cell-mediated alloresistance without requiring host T-cell depletion, permitting the induction of permanent mixed chimerism and tolerance...
  23. ncbi Anti-CD40L monoclonal antibodies can replace anti-CD4 monoclonal antibodies for the nonmyeloablative induction of mixed xenogeneic chimerism
    Hiroshi Ito
    Bone Marrow Transplantation Section, Transplantation Biology Research Center, Massachusetts General Hospital Harvard Medical School, Boston, 02129, USA
    Transplantation 82:251-7. 2006
    ..We have recently demonstrated that anti-CD40L mAb treatment is sufficient to completely overcome CD4 cell-mediated resistance to allogeneic marrow engraftment and rapidly induce CD4 cell tolerance in an allogeneic combination...
  24. ncbi Anti-tumour response despite loss of donor chimaerism in patients treated with non-myeloablative conditioning and allogeneic stem cell transplantation
    Bimalangshu R Dey
    Department of Medicine Harvard Medical School Boston, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
    Br J Haematol 128:351-9. 2005
    ..Immunological mechanisms that correlated with rejection of the graft may have a role in anti-tumour responses via a cell or cytokine-mediated pathway...
  25. ncbi Homeostatic expansion and phenotypic conversion of human T cells depend on peripheral interactions with APCs
    Takashi Onoe
    Transplantation Biology Research Center, Massachusetts General Hospital, and Department of Surgery, Harvard Medical School, Boston, MA 02129, USA
    J Immunol 184:6756-65. 2010
    ..Because lymphopenia affects clinical outcomes, this model, which will allow detailed investigation of the effects of lymphopenia in patients, is of clinical significance...
  26. ncbi Abnormal regulatory and effector T cell function predispose to autoimmunity following xenogeneic thymic transplantation
    Yasuhiro Fudaba
    Department of Surgery, Transplantation Biology Research Center, Massachusetts General Hospital Harvard Medical School, Boston, MA 02129, USA
    J Immunol 181:7649-59. 2008
    ..Regulatory cell function is enhanced and negative selection of host-specific thymocytes may potentially also be improved by coimplantation of recipient thymic epithelial cells in the thymus xenograft...
  27. ncbi High antigen levels do not preclude B-cell tolerance induction to alpha1,3-Gal via mixed chimerism
    Fabienne Haspot
    Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, 149 5102 13th Street, Boston, MA 02129, USA
    Xenotransplantation 15:313-20. 2008
    ....
  28. ncbi CTLA-4 on alloreactive CD4 T cells interacts with recipient CD80/86 to promote tolerance
    Josef Kurtz
    Bone Marrow Transplantation Section, Transplantation Biology Research Center, Massachusetts General Hospital Harvard Medical School, Boston, MA 02129, USA
    Blood 113:3475-84. 2009
    ..This tolerance is independent of regulatory T cells and culminates in the deletion of directly alloreactive CD4 T cells...
  29. ncbi 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
    Yong Zhao
    Bone Marrow Transplantation Section, Transplantation Biology Research Center, Department of Surgery, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02129, USA
    Transplantation 75:1832-40. 2003
    ....
  30. ncbi Role of indirect allo- and autoreactivity in anti-tumor responses induced by recipient leukocyte infusions (RLI) in mixed chimeras prepared with nonmyeloablative conditioning
    Marie-Therese Rubio
    Transplantation Biology Research Center, Bone Marrow Transplantation Section, Massachusetts General Hospital/Harvard Medical School, MGH-East, Bldg. 149-5102 13th Street, Boston, MA 02129, USA
    Clin Immunol 120:33-44. 2006
    ..Thus, anti-tumor cytotoxic responses are generated following complex interactions between recipient APCs presenting donor and recipient antigens and host-type CD4+, CD8+ and CD4-CD8- cells...
  31. ncbi Early host CD8 T-cell recovery and sensitized anti-donor interleukin-2-producing and cytotoxic T-cell responses associated with marrow graft rejection following nonmyeloablative allogeneic bone marrow transplantation
    Annette B Kraus
    Bone Marrow Transplantation Section, Transplantation Biology Research Center, Department of Surgery, Massachusetts General Hospital/Harvard Medical School, Boston, Mass, USA
    Exp Hematol 31:609-21. 2003
    ..These data are the first to demonstrate sensitization of recipient anti-donor IL-2-producing cells in association with human marrow allograft rejection...
  32. ncbi Marked prolongation of porcine renal xenograft survival in baboons through the use of alpha1,3-galactosyltransferase gene-knockout donors and the cotransplantation of vascularized thymic tissue
    Kazuhiko Yamada
    Transplantation Biology Research Center, Massachusetts General Hospital, Boston, Massachusetts 02129, USA
    Nat Med 11:32-4. 2005
    ..We have achieved life-supporting pig-to-baboon renal xenograft survivals of up to 83 d with normal creatinine levels...
  33. ncbi B-cell extrinsic CR1/CR2 promotes natural antibody production and tolerance induction of anti-alphaGAL-producing B-1 cells
    Ichiro Shimizu
    Bone Marrow Transplantation Section, Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, USA
    Blood 109:1773-81. 2007
    ..Our results suggest a possible role for follicular dendritic cells that pick up immune complexes via CR1/CR2 receptors in the tolerization of B-1b cells...
  34. ncbi Mechanisms of transplantation tolerance in animals and humans
    Megan Sykes
    Bone Marrow Transplantation Section, Transplantation Biology Research Center, Surgical Service, Massachusetts General Hospital Harvard Medical School, Boston, MA 02129, USA
    Transplantation 87:S67-9. 2009
    ..Hematopoietic cell transplantation has shown preliminary success for intentional tolerance induction in pilot clinical trials. The mechanisms of tolerance in these trials and the animal studies leading up to them are discussed...
  35. ncbi Regulatory T-cell recovery in recipients of haploidentical nonmyeloablative hematopoietic cell transplantation with a humanized anti-CD2 mAb, MEDI-507, with or without fludarabine
    Juanita Shaffer
    Transplantation Biology Research Center, Bone Marrow Transplantation Section, Massachusetts General Hospital Harvard Medical School, Boston, MA 02129, USA
    Exp Hematol 35:1140-52. 2007
    ....
  36. ncbi 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
    Bimalangshu R Dey
    Bone Marrow Transplantation Program Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, USA
    Biol Blood Marrow Transplant 9:320-9. 2003
    ....
  37. ncbi Occurrence of specific humoral non-responsiveness to swine antigens following administration of GalT-KO bone marrow to baboons
    Adam Griesemer
    Transplantation Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA
    Xenotransplantation 17:300-12. 2010
    ....
  38. ncbi Nonmyeloablative haploidentical stem-cell transplantation using anti-CD2 monoclonal antibody (MEDI-507)-based conditioning for refractory hematologic malignancies
    Thomas R Spitzer
    Bone Marrow Transplantation Program/Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114-1126, USA
    Transplantation 75:1748-51. 2003
    ..Nonmyeloablative preparative therapy with MEDI-507 and haploidentical SCT have led to the reliable induction of at least transient mixed chimerism as a potential platform for adoptive cellular immunotherapy...
  39. ncbi Peritoneal cavity B cells are precursors of splenic IgM natural antibody-producing cells
    Toshiyasu Kawahara
    Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA
    J Immunol 171:5406-14. 2003
    ..These findings demonstrate that peritoneal cavity Mac-1(+) B-1 cells are precursors of Mac-1(-) splenic IgM Ab-secreting cells...
  40. ncbi NK cell recovery, chimerism, function, and recognition in recipients of haploidentical hematopoietic cell transplantation following nonmyeloablative conditioning using a humanized anti-CD2 mAb, Medi-507
    Christian Koenecke
    Department of Surgery, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts 02129, USA
    Exp Hematol 31:911-23. 2003
    ..Our data also raise questions about the applicability of observations made with NK cell clones to the bulk NK cell repertoire in humans...
  41. ncbi Expression of chemokines in GVHD target organs is influenced by conditioning and genetic factors and amplified by GVHR
    Markus Y Mapara
    Transplantation Biology Research Center, Bone Marrow Transplantation Section, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02129, USA
    Biol Blood Marrow Transplant 12:623-34. 2006
    ....
  42. ncbi Clinical relevance of recipient leukocyte infusion as antitumor therapy following nonmyeloablative allogeneic hematopoietic cell transplantation
    Toshiki I Saito
    Bone Marrow Transplantation Section, Transplantation Biology Research Center, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts 02129, USA
    Exp Hematol 34:1271-7. 2006
    ..In contrast to DLI, RLI leads to donor cell rejection without the risk of GVHD. CONCLUSION: Together, these data reinforce the clinical potential of RLI therapy as a new HCT strategy that does not carry the risk of GVHD...
  43. ncbi Tolerance induction in clinical transplantation
    Thomas Fehr
    Transplantation Biology Research Center, Bone Marrow Transplantation Section, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA
    Transpl Immunol 13:117-30. 2004
    ..We summarize and discuss the results of these trials and suggest goals for further studies for the development tolerance protocols applicable for a broad population of allograft recipients...
  44. ncbi Long-term follow-up of recipients of combined human leukocyte antigen-matched bone marrow and kidney transplantation for multiple myeloma with end-stage renal disease
    Thomas R Spitzer
    Department of Medicine, Bone Marrow Transplant Unit, Massachusetts General Hospital, Boston, MA 02114, USA
    Transplantation 91:672-6. 2011
    ....
  45. ncbi Antitumor effect of donor marrow graft rejection induced by recipient leukocyte infusions in mixed chimeras prepared with nonmyeloablative conditioning: critical role for recipient-derived IFN-gamma
    Marie-Therese Rubio
    Transplantation Biology Research Center, Bone Marrow Transplantation Section, MGH-East Bldg 149-5102, Massachusetts General Hospital, Harvard Medical School, 13th Street, Boston, MA 02129, USA
    Blood 102:2300-7. 2003
    ..A novel approach to achieving anti-tumor effects without the risk of GVHD is suggested...
  46. ncbi Induction of human T-cell tolerance to porcine xenoantigens through mixed hematopoietic chimerism
    Ping Lan
    Transplantation Biology Research Center, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02129, USA
    Blood 103:3964-9. 2004
    ..This study proves the principle that porcine chimerism induces tolerance of xenoreactive human T cells...
  47. ncbi Antigen-specific human T-cell responses and T cell-dependent production of human antibodies in a humanized mouse model
    Noriko Tonomura
    Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, MGH East, Boston, MA 02129, USA
    Blood 111:4293-6. 2008
    ..These results confirm that a functional human immune system can be established in immunodeficient mice through cotransplantation of human fetal thymus/liver tissues and CD34(+) hematopoietic stem/progenitor cells...
  48. ncbi Mixed chimerism induces donor-specific T-cell tolerance across a highly disparate xenogeneic barrier
    Masahiro Abe
    Transplantation Biology Research Center, Surgical Service, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02129, USA
    Blood 99:3823-9. 2002
    ..Thus, mixed chimerism is capable of inducing tolerance in a highly disparate xenogeneic combination and may have clinical potential to prevent xenograft rejection. (Blood. 2002;99:3823-3829)..
  49. ncbi Mixed hematopoietic chimerism allows cure of autoimmune diabetes through allogeneic tolerance and reversal of autoimmunity
    Boris Nikolic
    Renal Unit, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, USA
    Diabetes 53:376-83. 2004
    ..Thus, mixed hematopoietic chimerism induces tolerance to donor islets and reverses established autoimmunity in diabetic NOD mice...
  50. ncbi An inflammatory checkpoint regulates recruitment of graft-versus-host reactive T cells to peripheral tissues
    Ronjon Chakraverty
    Transplantation Biology Research Center, Bone Marrow Transplantation Section, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA
    J Exp Med 203:2021-31. 2006
    ..Our studies help to explain the paradox whereby GVH-reactive T cells can mediate graft-versus-leukemia responses without inducing GVHD in established MCs...
  51. ncbi Manipulating the immune system for anti-tumor responses and transplant tolerance via mixed hematopoietic chimerism
    Carrie Gibbons
    Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA
    Immunol Rev 223:334-60. 2008
    ....
  52. ncbi Alloreactive CD8 T cell tolerance requires recipient B cells, dendritic cells, and MHC class II
    Thomas Fehr
    Transplantation Biology Research Center, Massachusetts General Hospital Harvard Medical School, Boston, MA 02129, USA
    J Immunol 181:165-73. 2008
    ..We demonstrate a critical role for recipient MHC class II, B cells, and dendritic cells in a pathway culminating in deletional tolerance of peripheral alloreactive CD8 cells...
  53. ncbi Porcine thymic grafts protect human thymocytes from HIV-1-induced destruction
    David Hongo
    Bone Marrow Transplantation Section, Transplantation Biology Research Center, Massachusetts General Hospital Harvard Medical School, Boston, MA 02129, USA
    J Infect Dis 196:900-10. 2007
    ..The model allows analysis of the mechanisms of HIV-mediated thymic dysfunction...
  54. ncbi Mouse retrovirus mediates porcine endogenous retrovirus transmission into human cells in long-term human-porcine chimeric mice
    Yong Guang Yang
    Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
    J Clin Invest 114:695-700. 2004
    ....
  55. ncbi Achieving tolerance in pig-to-primate xenotransplantation: reality or fantasy
    David H Sachs
    Transplantation Biology Research Center, Massachusetts General Hospital and Harvard Medical School Boston, Massachusetts, USA
    Transpl Immunol 21:101-5. 2009
    ....
  56. ncbi LAG-3, TGF-?, and cell-intrinsic PD-1 inhibitory pathways contribute to CD8 but not CD4 T-cell tolerance induced by allogeneic BMT with anti-CD40L
    Carrie L Lucas
    Transplantation Biology Research Center, Massachusetts General Hospital Harvard Medical School, Boston, MA, USA
    Blood 117:5532-40. 2011
    ..Finally, we uncovered a requirement for TGF-? signaling into T cells to achieve peripheral CD8 but not CD4 T-cell tolerance in this in vivo system...
  57. ncbi Persistence of donor-derived protein in host myeloid cells after induced rejection of engrafted allogeneic bone marrow cells
    Toshiki I Saito
    Bone Marrow Transplantation Section, Transplantation Biology Research Center, Massachusetts General Hospital Harvard Medical School, Boston, MA 02129, USA
    Exp Hematol 38:333-9. 2010
    ....
  58. ncbi Attenuation of phagocytosis of xenogeneic cells by manipulating CD47
    Hui Wang
    Bone Marrow Transplantation Section, Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, MGH East, Bldg 149 5102, 13th St, Boston, MA 02129, USA
    Blood 109:836-42. 2007
    ....
  59. ncbi T-cell P/E-selectin ligand alpha(1,3)fucosylation is not required for graft-vs-host disease induction
    Hyeon Seok Eom
    Transplantation Biology Research Center, Bone Marrow Transplantation Section, Massachusetts General Hospital Harvard Medical School, Boston, 02129, USA
    Exp Hematol 33:1564-73. 2005
    ..We hypothesized that Fuc-TIV(-/-)/Fuc-TVII(-/-) donor T cells might have reduced capacity to roll on vessels of inflamed target tissues and mediate graft-vs-host disease (GVHD)...
  60. ncbi Donor lymphocyte infusion-mediated graft-versus-leukemia effects in mixed chimeras established with a nonmyeloablative conditioning regimen: extinction of graft-versus-leukemia effects after conversion to full donor chimerism
    Markus Y Mapara
    Transplantation Biology Research Center, Bone Marrow Transplantation Section, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
    Transplantation 76:297-305. 2003
    ..The late loss of DLI-mediated GVL effects may reflect the eventual loss of donor-derived GVH-reactive CTL, which occurs in association with conversion to full donor chimerism...
  61. ncbi Fetal porcine thymus engraftment, survival and CD4 reconstitution in alphaGal-KO mice is impaired in the presence of high levels of antibodies against alphaGal
    Jose-Ignacio Rodriguez-Barbosa
    Transplantation Biology Research Center, Bone Marrow Transplantation Section, Surgical Service, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02129, USA
    Xenotransplantation 10:24-40. 2003
    ....
  62. ncbi Human natural regulatory T cell development, suppressive function, and postthymic maturation in a humanized mouse model
    Takashi Onoe
    Department of Surgery, Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
    J Immunol 187:3895-903. 2011
    ..These studies demonstrate the utility of this humanized mouse model for the study of human Treg ontogeny, immunobiology and therapy...
  63. ncbi NK cell tolerance in mixed allogeneic chimeras
    Yong Zhao
    Bone Marrow Transplantation Section, Transplantation Biology Research Center, Surgical Service, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02129, USA
    J Immunol 170:5398-405. 2003
    ..Thus, the present studies demonstrate that NK cells in mixed chimeras are stably tolerant to both donor and host Ags, by mechanisms that are as yet unexplained...
  64. ncbi Xenogeneic thymus transplantation in a pig-to-baboon model
    Anette Wu
    Transplantation Biology Research Center, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02129, USA
    Transplantation 75:282-91. 2003
    ..CONCLUSIONS: Porcine thymic tissue is able to induce xenogeneic hyporesponsiveness. More efficient thymic engraftment may allow this approach to induce xenograft tolerance...
  65. ncbi Elimination of porcine hemopoietic cells by macrophages in mice
    Masahiro Abe
    Bone Marrow Transplantation Section, Transplantation Biology Research Center, Surgical Service, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02129, USA
    J Immunol 168:621-8. 2002
    ..Because injection of M-liposomes i.v. mainly depletes splenic macrophages and liver Kupffer cells, the spleen and/or liver are likely the primary sites of porcine cell clearance in vivo...
  66. ncbi Non-myeloblative induction of mixed hematopoietic chimerism: application to transplantation tolerance and hematologic malignancies in experimental and clinical studies
    Megan Sykes
    Massachusetts General Hospital, MGH East, Building 149/5102, 13th Street, Boston, MA 02129, USA
    Cancer Treat Res 110:79-99. 2002
  67. ncbi Murine CD4 T cells selected in a highly disparate xenogeneic porcine thymus graft do not show rapid decay in the absence of selecting MHC in the periphery
    Jose-Ignacio Rodriguez-Barbosa
    Transplantation Biology Research Center, Bone Marrow Transplantation Section, Surgical Service, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02129, USA
    J Immunol 169:6697-710. 2002
    ..Our results support the interpretation that xenogeneic thymic transplantation is a feasible strategy to reconstitute CD4 T cells and render recipients tolerant of a xenogeneic donor...
  68. ncbi Local irradiation enhances congenic donor pluripotent hematopoietic stem cell engraftment similarly in irradiated and nonirradiated sites
    Hiroshi Ito
    Transplantation Biology Research Center, Bone Marrow Transplantation Section, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02129, USA
    Blood 103:1949-54. 2004
    ..Our study suggests that local proliferation of donor PHSCs in mice receiving local irradiation rapidly leads to a systemic increase in donor PHSC engraftment...
  69. ncbi Induction of robust cellular and humoral virus-specific adaptive immune responses in human immunodeficiency virus-infected humanized BLT mice
    Diana M Brainard
    Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA
    J Virol 83:7305-21. 2009
    ....
  70. ncbi Donor lymphocyte infusions mediate superior graft-versus-leukemia effects in mixed compared to fully allogeneic chimeras: a critical role for host antigen-presenting cells
    Markus Y Mapara
    Transplantation Biology Research Center, Bone Marrow Transplantation Section, Massachusetts General Hospital, Harvard Medical School, Boston 02129, USA
    Blood 100:1903-9. 2002
    ..Thus, the induction of mixed chimerism followed by delayed DLI provides an approach to inhibiting GVHD that optimizes GVL effects...
  71. ncbi Graft-versus-host disease can be separated from graft-versus-lymphoma effects by control of lymphocyte trafficking with FTY720
    Yong-Mi Kim
    Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02129, USA
    J Clin Invest 111:659-69. 2003
    ..These results establish a potential new immunotherapeutic approach to separating graft-versus-leukemia effects from GvHD...
  72. ncbi Fluctuating lymphocyte chimerism, tolerance and anti-tumor response in a patient with refractory lymphoma receiving nonmyeloablative conditioning and a haploidentical related allogeneic bone marrow transplant
    Han C Toh
    Bone Marrow Transplant Program, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA
    Cytokines Cell Mol Ther 7:43-7. 2002
    ..Eventual lymphoma relapse temporally correlated with a generalised immunosuppressed state...
  73. ncbi CD154 blockade for induction of mixed chimerism and prolonged renal allograft survival in nonhuman primates
    Tatsuo Kawai
    Department of Surgery, Transplantation Unit, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA
    Am J Transplant 4:1391-8. 2004
    ..Modification of the original mixed chimerism approach, by the addition of costimulatory blockade, has been shown to enhance mixed chimerism and induce renal allograft tolerance with less morbidity in nonhuman primates...
  74. ncbi Tolerance in mixed chimerism - a role for regulatory cells?
    Josef Kurtz
    Bone Marrow Transplantation Section, Transplantation Biology Research Center, Massachusetts General Hospital/Harvard Medical School, MGH East, Bldg. 149-5102 13(th) Street, Boston, MA 02129, USA
    Trends Immunol 25:518-23. 2004
    ..However, in situations where high levels of donor chimerism cannot be established or sustained, control of immune responsiveness can be achieved through additional mechanisms, including regulatory T cells...
  75. ncbi Induction of kidney allograft tolerance after transient lymphohematopoietic chimerism in patients with multiple myeloma and end-stage renal disease
    Leo H Buhler
    Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA
    Transplantation 74:1405-9. 2002
    ....
  76. ncbi Position paper of the Ethics Committee of the International Xenotransplantation Association
    Megan Sykes
    Transplantation Biology Research Center, Massachusetts General Hospital Harvard Medical School, MGH East, 13th Street, Boston, MA 02129, USA
    Transplantation 78:1101-7. 2004
    ..Some of the most pressing ethical issues are discussed, and the position of the Ethics Committee of the International Xenotransplantation Association is presented...
  77. ncbi Mixed hematopoietic chimerism for the simultaneous induction of T and B cell tolerance
    Megan Sykes
    Bone Marrow Transplant Section, Transplantation Biology Research Center, Massachusetts General Hospital Harvard Medical School, Boston, MA 02129, USA
    Transplantation 79:S28-9. 2005
    ..We present evidence that different mechanisms are involved in the tolerization of the preexisting and newly-developing antibody-secreting cells...
  78. ncbi Lineage-negative side-population (SP) cells with restricted hematopoietic capacity circulate in normal human adult blood: immunophenotypic and functional characterization
    Frederic I Preffer
    Department of Pathology, Transplantation Biology Research Center, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
    Stem Cells 20:417-27. 2002
    ..Thus, human blood SP cells, although rare, may serve as a source of selected leukocyte progenitor cells. The immunophenotype of circulating SP cells may provide clues to their seeding and homing capacity...
  79. ncbi Position paper of the Ethics Committee of the International Xenotransplantation Association
    Megan Sykes
    Transplantation Biology Research Center, Massachusetts General Hospital Harvard Medical School, Boston, MA 02129, USA
    Xenotransplantation 10:194-203. 2003
    ..Some of the most pressing ethical issues are discussed, and the position of the Ethics Committee of the International Xenotransplantation Association is presented...
  80. ncbi Donor-derived interferon gamma separates graft-versus-leukemia effects and graft-versus-host disease induced by donor CD8 T cells
    Yong Guang Yang
    Bone Marrow Transplantation Section, Transplantation Biology Research Center, Surgical Service, Massachusetts General Hospital Harvard Medical School, Boston, MA 02129, USA
    Blood 99:4207-15. 2002
    ..These data show for the first time that GVHD-inducing activity and GVL effects of allogeneic CD8 T cells can be separated by a single cytokine, IFN-gamma. (Blood. 2002;99:4207-4215)..
  81. ncbi Commentary: World Health Assembly resolution 57.18 on xenotransplantation
    Megan Sykes
    Ethics Committee of the International Xenotransplantation Association
    Transplantation 79:636-7. 2005
  82. ncbi Hematopoietic cell transplantation for tolerance induction: animal models to clinical trials
    Megan Sykes
    Bone Marrow Transplantation Section, Transplantation Biology Research Center, Surgical Service, Massachusetts General Hospital Harvard Medical School, Boston, MA 02129, USA
    Transplantation 87:309-16. 2009
    ....
  83. ncbi World Health Organization resolution on xenotransplantation
    Megan Sykes
    Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA
    Xenotransplantation 11:224-5. 2004
  84. ncbi 2007 IXA Presidential Address. Progress toward an ideal source animal: opportunities and challenges in a changing world
    Megan Sykes
    Bone Marrow Transplantation Section, Transplantation Biology Research Center, Massachusetts General Hospital Harvard Medical School, Boston, MA 02129, USA
    Xenotransplantation 15:7-13. 2008
    ....
  85. ncbi Mechanisms of tolerance induced via mixed chimerism
    Megan Sykes
    Transplantation Biology Research Center, Department of Surgery, Massachusetts General Hospital Harvard Medical School, Boston, MA 02129, USA
    Front Biosci 12:2922-34. 2007
    ..An emerging understanding of these mechanisms, along with the development of new immunosuppressive reagents, is allowing advancement toward clinical application of this approach...
  86. ncbi Organ transplantation--how much of the promise has been realized?
    Robert I Lechler
    Guy's King's and St. Thomas's Medical School, King's College London, Hodgkin Building, Guy's Campus, London SE1 9RT, UK
    Nat Med 11:605-13. 2005
    ..Developing methods to induce transplant tolerance, as a means to improve graft outcomes and eliminate the requirement for immunosuppression, and expanding the pool of organs for transplantation are the major challenges of the field...
  87. ncbi Minimal conditioning required in a murine model of T cell depletion, thymic irradiation and high-dose bone marrow transplantation for the induction of mixed chimerism and tolerance
    Thomas Wekerle
    Division of Transplantation, Department of Surgery, Vienna General Hospital, Wahringer Gurtel 18, 1090 Austria
    Transpl Int 15:248-53. 2002
    ..However, the dose of TCD mAbs and hence the duration of recipient T cell depletion could be safely reduced and thus the potential toxicity of the conditioning regimen lowered...
  88. ncbi Short-term immunosuppression facilitates induction of mixed chimerism and tolerance after bone marrow transplantation without cytoreductive conditioning
    Peter Blaha
    Division of Transplantation, Department of Surgery, Vienna General Hospital, Medical University of Vienna, Vienna, Austria
    Transplantation 80:237-43. 2005
    ..Thus, IS might help in the further development of noncytoreductive chimerism protocols...
  89. ncbi Protecting the host naturally
    Megan Sykes
    Nat Med 11:1164-5. 2005
  90. ncbi Long-term survival of xenogeneic heart grafts achieved by costimulatory blockade and transient mixed chimerism
    Masanori Murakami
    Department of Surgery and Clinical Science, Yamaguchi University, Graduate School of Medicine, Japan
    Transplantation 82:275-81. 2006
    ..Transplantation of xenogeneic bone marrow cells under costimulatory blockade at the time of heart transplantation may induce transplantation tolerance...
  91. ncbi Nonmyeloablative bone marrow transplantation: Infectious complications in 65 recipients of HLA-identical and mismatched transplants
    Andrew Daly
    Allogeneic Bone Marrow Transplant Program, Princess Margaret Hospital University Health Network, University of Toronto, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9
    Biol Blood Marrow Transplant 9:373-82. 2003
    ..We conclude that a quantitative T-cell deficiency in these extensively T-cell depleted patients may be a risk factor for infection, even in the absence of graft-versus-host disease...
  92. ncbi The influence of immunosuppressive drugs on tolerance induction through bone marrow transplantation with costimulation blockade
    Peter Blaha
    Division of Transplantation, Department of Surgery, Vienna General Hospital, University of Vienna, Austria
    Blood 101:2886-93. 2003
    ..These results should facilitate clinical application of this tolerance strategy...
  93. ncbi Role of VLA-4 and VLA-5 in ex vivo maintenance of human and pig hematopoiesis in human stroma-supported long-term cultures
    Maria A Giovino
    Immerge BioTherapeutics Inc, Cambridge, Mass, USA
    Exp Hematol 33:363-70. 2005
    ..Thus, VLA-5 may provide a potential target for developing approaches to improve porcine hematopoiesis in human recipients...
  94. ncbi CTLA4Ig promotes the induction of hematopoietic chimerism and tolerance independently of Indoleamine-2,3-dioxygenase
    Ines Pree
    Division of Transplantation, Department of Surgery, Vienna General Hospital, Medical University of Vienna, Vienna, Austria
    Transplantation 83:663-7. 2007
    ..Thus, IDO does not play a critical role in the induction or maintenance of chimerism and tolerance in a CTLA4Ig-based BMT model...
  95. ncbi Induction of mixed vs full chimerism to potentiate GVL effects after bone-marrow transplantation
    Markus Y Mapara
    Division of Hematology/Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA
    Methods Mol Med 109:469-74. 2005
    ..Induction of mixed hematopoietic chimerism using the method described below allows analysis of these interactions between host APC and donor T-cells...
  96. ncbi Central tolerance to myogenic cell transplants does not include muscle neoantigens
    Geoffrey Camirand
    Internal Medicine, Yale University School of Medicine, New Haven, CT, USA
    Transplantation 85:1791-801. 2008
    ..However, given its immunogenicity, we asked whether central tolerance to donor major histocompatibility complex would allow long-term expression of dystrophin, a tissue-specific neoantigen in dystrophic recipients...
  97. ncbi Stem cell activity of porcine c-kit+ hematopoietic cells
    Annie C Le Guern
    BioTransplant, Incorporated, Charlestown, Mass, USA
    Exp Hematol 31:833-40. 2003
    ..CONCLUSION: The present study demonstrates that c-kit is an essential marker of both long-term-repopulating HSCs and progenitor cells with early engraftment capacity...