Role of the thymus and kidney graft in the maintenance of tolerance to heart grafts in miniature swine.
BACKGROUND
The authors have examined the mechanism whereby co-transplantation of a kidney and heart from the same donor induces and maintains tolerance to both organs in miniature swine.


METHODS
Transplants were performed across a major histocompatibility complex class I mismatch, and recipients received cyclosporine for 12 days. Group 1 animals received heart transplants alone (n=5), and all other groups received both heart and kidney allografts. Group 2 animals received no further intervention (n=2). Group 3 animals underwent transplant nephrectomy 8 days after heart and kidney co-transplantation (n=2). Group 4 animals underwent transplant nephrectomy 100 days after co-transplantation (n=2). Skin grafts were placed on group 4 animals, on one group 3 animal, and on two animals from group 2. Group 5 animals underwent thymectomy 100 days after co-transplantation (n=4).


RESULTS
Group 1 animals developed cardiac allograft vasculopathy (CAV) and rejection. Group 2 animals never developed CAV and demonstrated in vitro donor-specific unresponsiveness. Group 3 animals suffered CAV and rejection. Group 4 animals developed CAV without concomitant donor-specific cell-mediated lympholysis reactivity, interstitial rejection, or cessation of graft function. Skin grafts on group 3 and group 4 animals led to fulminant rejection of heart and skin grafts, in contrast to grafts on group 2 animals that had no in vivo effect. Group 5 animals developed CAV but no significant increase in interstitial infiltrates.


CONCLUSIONS
Both the kidney and thymus were necessary for maintenance of tolerance to heart allografts.
Transplantation Biology Research Center, Massachusetts General Hospital-Harvard Medical School, 13th Street, Boston, MA, USA.
Joshua D
JD
Mezrich
Louis C
LC
Benjamin
Jessica A
JA
Sachs
Stuart L
SL
Houser
Parsia A
PA
Vagefi
David H
DH
Sachs
Joren C
JC
Madsen
Kazuhiko
K
Yamada
D000818:Animals; D016572:Cyclosporine / Q000627:therapeutic use; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology; D016027:Heart Transplantation / Q000276:immunology* / Q000473:pathology; D006650:Histocompatibility Testing; D049690:History, Ancient; D007108:Immune Tolerance; D007111:Immunity, Cellular; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology; D007959:Lymphocyte Culture Test, Mixed; D009392:Nephrectomy; D013552:Swine; D013556:Swine, Miniature; D013950:Thymus Gland / Q000637:transplantation*; D014184:Transplantation, Homologous / Q000276:immunology* / Q000473:pathology
D007166:Immunosuppressive Agents; D016572:Cyclosporine