Induction of long-term survival of hamster heart xenografts in rats.
The aim of this study was to determine the mechanisms responsible for concordant xenograft rejection using the hamster-to-rat heart graft model. Even though it was known that rat CD4 positive T cells proliferated to hamster stimulators in mixed lymphocyte reactions, the depletion of CD4 positive T cells in rat recipients did not lead to an extension of xenograft survival. Suppression of T cell immunity using other monoclonal antibodies or cyclosporine also failed to improve survival. Only by depleting complement with cobra-venom factor could hamster xenograft survival be prolonged, and long-term survival was achieved by combining CsA with COF. High-antibody titers to hamster cells were found after transplantation of hamster hearts, and evidence is presented that rejection of these "concordant" xenografts is mediated primarily by antibody-complement mechanisms. The antihamster antibodies were produced in the absence of T cell help, which suggests that antibody-mediated graft destruction cannot be inhibited by suppression or depletion of T cells. Pharmacologic depletion of complement for the clinical application of concordant xenografts is a promising avenue of future research.
van den Bogaerde
J
J
Department of Surgery, Cambridge University Medical School, Addenbrookes Hospital, United Kingdom.
Aspinall
R
R
Wang
M W
MW
Cary
N
N
Lim
S
S
Wright
L
L
White
D
D
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D015704:CD4 Antigens / Q000276:immunology; D003165:Complement System Proteins / Q000276:immunology; D006224:Cricetinae; D003524:Cyclosporins / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D004546:Elapid Venoms / Q000627:therapeutic use; D006084:Graft Rejection / Q000187:drug effects; D006085:Graft Survival; D016027:Heart Transplantation / Q000276:immunology* / Q000401:mortality; D008212:Lymphocyte Depletion; D051381:Rats; D013601:T-Lymphocytes / Q000276:immunology; D014181:Transplantation Immunology; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D003524:Cyclosporins; D004546:Elapid Venoms; D003165:Complement System Proteins