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.
| Lima, Brian; Gleit, Zachary L; Cameron, Andrew M et al. (2003) Engraftment of quiescent progenitors and conversion to full chimerism after nonmyelosuppressive conditioning and hematopoietic cell transplantation in miniature swine. Biol Blood Marrow Transplant 9:571-82 |
| Gleit, Zachary L; Fuchimoto, Yasushi; Yamada, Kazuhiko et al. (2002) Variable relationship between chimerism and tolerance after hematopoietic cell transplantation without myelosuppressive conditioning. Transplantation 74:1535-44 |
| Gleit, Zachary L; Cameron, Andrew M; Fuchimoto, Yasushi et al. (2002) Persistent chimerism despite antidonor MHC in vitro responses in miniature swine following allogeneic hematopoietic cell transplantation. Transplantation 74:1260-6 |
| Fuchimoto, Y; Gleit, Z L; Huang, C A et al. (2001) Skin-specific alloantigens in miniature swine. Transplantation 72:122-6 |
