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.