INDUCTION OF TOLERANCE TO HEART ALLOGRAFTS IN RATS USING POSTTRANSPLANT TOTAL LYMPHOID IRRADIATION AND ANTI-T CELL ANTIBODIES

This study examined whether posttransplant anti-T cell monoclonal or p olyclonal antibody therapy could provide a window of treatment to allo w posttransplant total lymphoid irradiation (TLI) to induce tolerance. These experiments were conducted in a high responder strain combinati on of an ACI cardiac allograft into a Lewis rat. In this situation, tr eatment with antibody or posttransplant TLI alone is insufficient to i nduce tolerance, while similar treatments alone have been shown to ind uce tolerance in low responder strains. The affects of three anti-T ce ll therapies were compared: anti-CD4 mAb therapy, anti-CD3 mAb, and ra bbit antithymocyte globulin (RATG). None of these antibody therapies a lone prolonged graft survival indefinitely. Combining anti-CD4 therapy with posttransplant TLI markedly delayed rejection but failed to indu ce long-term graft survival. Tolerance could be induced by a combinati on of antipan T cell antibody (anti-CDS) and TLI, and, all grafts surv ived beyond 100 days. RATG failed to prevent graft rejection when used alone or in combination with TLI. However, posttransplant therapy wit h a combination of RATG, TLI, and single-donor blood transfusion resul ted in graft survival beyond 100 days. Recipients bearing long-term do nor grafts rejected third-party (PVG) grafts within 2 weeks. Low densi ty donor bone marrow cells used instead of a blood transfusion did not facilitate tolerance. The results indicate that monoclonal or polyclo nal anti-pan T cell antibodies, TLI, and a donor blood cell infusion f unction synergistically in facilitating tolerance to allografts in the posttransplant period.