INDUCTION OF XENOGRAFT TOLERANCE VIA THYMIC TRANSPLANTS

Massachusetts General Hospital, Boston MA

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Abstract

Recent studies in mice have demonstrated that thymic xenotransplantation from miniature-swine donors can confer specific tolerance to donor antigens while supporting a competent immune system. I propose to examine the hypothesis that transplantation of miniature-swine thymic tissue can similarly confer tolerance to swine antigens in primates and that this will permit tolerance of whole-organ xenotransplants. This will be accomplished by optimizing a protocol for thymic transplantation into baboons and studying various indices of tolerance and immunocompetence in baboon recipients of thymic xenografts, culminating in whole-organ xeno-transplantation. These studies will have important implications for tolerance in both allo- and xeno-transplantation in humans, potentially providing a solution for the shortage of organs available for transplantation and minimizing the need for powerful inununosuppressive drugs. They may also have implications for treatment of HIV infection.