Subject(s)
Graft Survival/immunology , Heart Transplantation/immunology , Major Histocompatibility Complex , Transplantation, Heterologous/immunology , Transplantation, Homologous/immunology , Animals , Crosses, Genetic , Female , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C3H , Mice, Inbred C57BL , Mice, Inbred CBA , Mice, Inbred DBA , Rats , Rats, Inbred Lew , Species Specificity , Transplantation, HeterotopicABSTRACT
The immunologic mechanisms involved in the destruction of murine cardiac allografts were evaluated using MHC-deficient mice. Specifically, we examined the survival of immediately vascularized heterotopic adult cardiac grafts deficient in MHC class I, MHC class II, or both MHC class I and II antigens following transplantation to allogeneic hosts. We observed indefinite cardiac graft survival when donors lacked MHC class II or both MHC I and II antigens. In parallel experiments, we studied the survival of cardiac grafts harvested from normal donors in recipients severely depleted of either CD4 (class II-deficient mice) or CD8 (class I-deficient mice) T cells. Graft survival was dramatically prolonged in the absence of CD4 but not CD8 T cells. Collectively, our results demonstrate that the interaction of host CD4 T cells with donor class II antigens is critical to the rejection of murine cardiac grafts.
Subject(s)
Graft Survival/immunology , Heart Transplantation/immunology , Major Histocompatibility Complex/immunology , Transplantation, Heterotopic , Animals , CD8-Positive T-Lymphocytes/immunology , Coronary Vessels/physiology , Haplotypes , Histocompatibility Antigens Class I/immunology , Histocompatibility Antigens Class II/immunology , Histocompatibility Antigens Class II/metabolism , Lymphocyte Activation/immunology , Mice , Mice, Inbred Strains , Neck , T-Lymphocytes/immunology , Transplantation, Heterologous , Transplantation, HomologousABSTRACT
Freshly isolated allogenic pancreatic islets transplanted into the thymus of transiently immunosuppressed rats are not rejected but survive indefinitely while also inducing a state of specific unresponsiveness that permits survival of secondary donor-strain islets transplanted extrathymically. Since freshly isolated pancreatic islets contain intraislet antigen-presenting cells as well as endocrine cells it is unclear which cellular component is primarily responsible for mediating unresponsiveness. We therefore examined the impact of pretransplant in vitro culture (a maneuver which selectively depletes intraislet APCs) on the capacity of islet allografts to induce unresponsiveness after intrathymic implantation. APC-depleted pancreatic islets, which are known to have reduced immunogenicity, survived indefinitely in the thymus of allogeneic hosts whether or not brief immunosuppression was employed, but failed to promote survival of subsequent donor-strain islets transplanted to an extrathymic site. These findings emphasize the central role of APCs in the induction of transplantation tolerance in this model, and are consistent with the established role of this population in the development of T cell tolerance in the thymus.
