Transplantation tolerance and autoimmunity after xenogeneic thymus transplantation.

Abnormal regulatory and effector T cell function predispose to autoimmunity following xenogeneic thymic transplantation.

Porcine thymus grafts support robust murine and human thymopoiesis, generating a diverse T cell repertoire that is deleted of donor and host-reactive cells, achieving specific xenograft tolerance. Positive selection is mediated exclusively by the xenogeneic thymic MHC. Although thymectomized, T cell-depleted normal mice usually remain healthy following xenogeneic thymic transplantation, thymus-...

Xenogeneic Thymus Transplantation Pathogenesis of Autoimmunity After

Cross-species bone marrow transplantation: evidence for tolerance induction, stem cell engraftment, and maturation of T lymphocytes in a xenogeneic stromal environment (rat----mouse)

Transplantation of untreated F344 rat bone marrow into irradiated B10 mouse recipients (non-TCD F344----B10) to produce fully xenogeneic chimeras resulted in stable xenogeneic lymphoid chimerism, ranging from 82% to 97% rat. Survival of animals was excellent, without evidence for GVH disease. The specificity of tolerance which resulted was highly donor-specific; MHC disparate third party mouse ...

Specific tolerance induction across a xenogeneic barrier: production of mixed rat/mouse lymphohematopoietic chimeras using a nonlethal preparative regimen

The development of safe methods for inducing donor-specific tolerance across xenogeneic barriers could potentially relieve the critical shortage of allograft donors that currently limits the applicability of organ transplantation. We report here that such tolerance can be induced in a xenogeneic combination (rat----mouse) using a nonmyeloablative and nonlethal preparative regimen. Successful in...

Thymus: a direct target tissue in graft-versus-host reaction after allogeneic bone marrow transplantation that results in abrogation of induction of self-tolerance.

Graft-versus-host reaction (GVHR) following allogeneic bone marrow (BM) transplantation was investigated by analyzing expression of antigen receptors on T cells specific for recipient antigens. GVHR chimeras were prepared by transplanting mixtures of splenic T cells and T-cell-depleted BM cells from B10 (I-E-, Mls-1b) or B10.AQR (I-E+, Mls-1b) mice into lethally irradiated AKR/J (I-E+, Mls-1a) ...