title: Mixed chimerism induces donor-specific T-cell tolerance across a highly disparate xenogeneic barrier.
abstract: Induction of tolerance is likely to be essential for successful xenotransplantation because immune responses across xenogeneic barriers are vigorous. Although mixed hematopoietic chimerism leads to stable donor-specific tolerance in allogeneic and closely related xenogeneic (eg, rat-to-mouse) combinations, the ability of this approach to induce tolerance across a highly disparate xenogeneic barrier has not yet been demonstrated. In this study, we investigated the immune responses of murine T cells that developed in mice with pre-established porcine hematopoietic chimerism. Our results show for the first time that induction of porcine hematopoietic chimerism can eliminate the development of antiporcine donor responses in a highly disparate xenogeneic species. Porcine hematopoietic chimeras showed donor-specific nonresponsiveness in the mixed lymphocyte reaction, lack of antidonor IgG antibody production, and acceptance of donor skin grafts. 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)
authors: Transplantation Biology Research Center, Surgical Service, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02129, USA.
authors: Masahiro
authors: M
authors: Abe
authors: Jin
authors: J
authors: Qi
authors: Megan
authors: M
authors: Sykes
authors: Yong-Guang
authors: YG
authors: Yang
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D006085:Graft Survival / Q000276:immunology; D006410:Hematopoiesis; D018380:Hematopoietic Stem Cell Transplantation; D007074:Immunoglobulin G / Q000096:biosynthesis; D007700:Kinetics; D007959:Lymphocyte Culture Test, Mixed; D008212:Lymphocyte Depletion; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008822:Mice, Transgenic; D016038:Skin Transplantation / Q000276:immunology; D013552:Swine; D013601:T-Lymphocytes / Q000276:immunology*; D018183:Transplantation Chimera; D023001:Transplantation Tolerance; D014183:Transplantation, Heterologous / Q000276:immunology*
chemical_list: D007074:Immunoglobulin G