Veto cells in transplantation tolerance.

Abstract

Advances in immunosuppressive management for transplantation have improved graft survival. However, lasting success will probably depend on the induction of donor-specific unresponsiveness, avoiding chronic immunosuppressive drug therapy and its debilitating side effects. Tolerance strategies have been developed in rodents, but applicability to human organ transplantation has not been achieved. We have established a preclinical allogeneic kidney transplant model in unrelated outbred rhesus monkeys and have investigated a tolerance-inducing strategy in which posttransplant administration of rabbit antithymocyte globulin and infusion of a subpopulation of donor bone marrow cells yields long-term 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 presented within the framework of a veto hypothesis.