Pre-transplant blood transfusion induces tolerance to hamster cardiac xenografts in athymic nude rats

The effects of pre-transplant blood transfusion vary from induction of anti bodies and accelerated graft rejection, to prolonged survival and even tole rance. The beneficial 'transfusion effect, in allotransplantation is believ ed to be merely T-cell mediated. In xenotransplantation, T-cell independent mechanisms form a major hurdle. In this study we investigated the effects of pre-transplant hamster blood transfusion on the survival of hamster card iac xenografts in T-cell deficient athymic nude rats. Nude rats rejected xe nografts after 3.8 +/- 0.5 d (n = 8), and immunocompetent Lewis rats after 4.0 +/- 0.5 d (n=8), following a similar IgM response (P=NS). Hamster blood transfusion 3 d before transplantation in nude rats led to an IgM response and long-term xenograft survival in 17/20. Timing was of importance: blood transfusion 7 d before transplantation resulted in 45% long-term xenograft survival (n=20). Injection of purified hamster erythrocytes, leukocytes or minced heart also led to survival of xenografts for > 100 d in nude rats, but not in all cases. Second xenografts transplanted to long-term survivors did not provoke an IigM response, and were accepted for > 100 d (n=4). Tra nsfer of serum from long-term survivors to untreated nude rats resulted in survival of xenografts for > 100 d (n=4). In Lewis rats pre-transplant bloo d transfusion induced hyperacute rejection of xenografts after 158 +/- 128 min (n=8, P <0.01). We conclude that pre-transplant hamster blood transfusi on can induce long-term survival of hamster cardiac xenografts in T-cell de ficient athymic nude rats. This blood transfusion effect is mediated by hum oral factors and can be transferred by serum. Elucidation of underlying mec hanisms might provide some insight into xenotransplantation nonresponsivene ss of T-cell independent immunefactors.