Complete withdrawal of immunosuppression in allograft recipients. A study in rhesus monkeys

The influence of pretransplant blood transfusions on kidney allograft survival after cessation of immunosuppressive treatment was studied in 11 rhesus monkeys. The animals were conditioned by three pretransplant blood transfusions. After an induction treatment with cyclosporine (CsA), the immunosuppression was stopped and the natural course of the graft was followed. In two monkeys long-term graft survival without immunosuppression was obtained (2.5 and 4.25 years). In a third monkey, permanent allograft acceptance was achieved after complete cessation of immunosuppression. The monkey is still alive with a well-functioning graft for more than 13 years after cessation of immunosuppression. This monkey had received CsA for 12 months, two MHC DR-matched blood transfusions, and no repeated mismatches between graft and blood transfusion donors. We speculate that blood transfusions may influence allograft function in two opposite ways. As reported previously in man, MHC class-II-matched transfusions appear to beneficially influence allograft survival. This effect seems to be negated by a mismatched MHC class II antigen in the blood transfusion donor which is also present in the organ donor -- a so-called repeated mismatch. Further studies in rhesus monkeys are required to confirm and extend these results. In the future, these observations might help in developing a protocol that opens up the possibility of cessation of immunosuppression in transplant patients.