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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32AI010306-01
Application #
2861277
Study Section
Special Emphasis Panel (ZRG1-IMB (01))
Program Officer
Prograis, Lawrence J
Project Start
1999-08-01
Project End
Budget Start
1999-08-01
Budget End
2000-07-31
Support Year
1
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199
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