VETO CELLS IN TRANSPLANTATION TOLERANCE

Advances in immunosuppressive management for transplantation have impr oved graft survival. However, lasting success will probably depend on the induction of donor-specific unresponsiveness, avoiding chronic imm unosuppressive drug therapy and its debilitating side effects. Toleran ce strategies have been developed in rodents, but applicability to hum an organ transplantation has not been achieved. We have established a preclinical allogeneic kidney transplant model in unrelated outbred rh esus monkeys and have investigated a tolerance-inducing strategy in wh ich posttransplant administration of rabbit antithymocyte globulin and infusion of a subpopulation of donor bone marrow cells yields long-te rm graft acceptance in the absence of chronic immunosuppressive drugs. Recent studies of the immunological mechanisms by which induction and maintenance of transplant tolerance is achieved in this model are pre sented within the framework of a veto hypothesis.