Tolerance across discordant xenogeneic barriers

Abstract

Abstract: In contrast to islet transplants, which appear to enjoy privileged survival when transplanted across some species barriers, organ xenografts are subject to vigorous immunologic rejection. Part of this rejection is immediate and is caused by the binding of natural antibodies to vascular endothelial cells, followed by activation of complement and coagulation factors, and hyperacute destruction of the graft. Such hyperacute rejection, in a pig‐to‐monkey kidney model that we are studying, can be avoided by removal of natural antibodies, which we have accomplished by absorption procedures. However, the cellular immune response to xenografts is also stronger than that to allografts. One might therefore expect the amount of nonspecific immunosuppression that would be required to avoid xenograft rejection to be so great that recipients would succumb to infectious complications. For this reason, we have pursued an approach to discordant xenografting involving the induction of tolerance though establishment of mixed lymphohematopoietic chimerism. We summarize here the present status of these experiments.