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.
Mezrich
Joshua D
JD
Transplantation Biology Research Center, Massachusetts General Hospital-Harvard Medical School, 13th Street, Boston, MA, USA.
Benjamin
Louis C
LC
Sachs
Jessica A
JA
Houser
Stuart L
SL
Vagefi
Parsia A
PA
Sachs
David H
DH
Madsen
Joren C
JC
Yamada
Kazuhiko
K
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