Studies on the participation of different T cell subsets in rat liver allograft rejection. Comparison of liver with heart graft.
In this study, we investigated which subsets of rat T cells (CD8+ vs. CD4+) are involved in the rejection of liver allografts by the in vivo administration of monoclonal antibody (OX-8 or OX-38, and W3/25 MAb) into thymectomized recipient Lewis (RTI(l)) rats prior to DA (RTI(a)) liver transplantation. We also compared the results of allograft survival of liver and heart transplants under the same experimental conditions. In order to deplete either CD8+ T cells or CD4+ T cells from recipient animals, 0.4 ml of OX-8 (ascitic form) or a 0.8 ml cocktail of MAb W3/25 and OX-38 (0.4 ml each) was injected into thymectomized recipient rats, respectively. Untreated Lewis rats consistently rejected donor DA liver grafts between 9 and 11 days (n = 7, 9.8 days +/- 1.1 days). In contrast, anti-CD8 MAb pretreatment extended the survival times of DA liver grafts for up to 40 days (n = 5, 26.8 days +/- 8.4 days). Furthermore, survival of DA liver grafts was significantly prolonged in Lewis rats that had been pretreated with anti-CD4 MAb (n = 7, 35.6 days +/- 17.9 days). Two out of seven recipient animals survived for more than 60 days. For heart transplantation, untreated Lewis rats rejected DA heart grafts between 6 and 8 days after operation (n = 6, 6.5 days +/- 1.2 days). Anti-CD4 MAb treatment prolonged heart graft survival for more than 60 days in all cases (n = 3, > 60 days). However, there was virtually no effect of anti-CD8 MAb treatment on heart graft survival (n = 4, 7.0 days +/- 0.9 days). These results suggested that when whole MHC disparity prevailed between donor and recipient, both subsets of T cells were required for the rejection of liver allografts and that class II reactive T cells predominantly mediated liver graft rejection. Furthermore, CD8+ T cells played a differential role in the rejection of rat liver and heart allograft.
Sumimoto
R
R
Department of Experimental Surgery, National Children's Medical Research Center, 3-35-31, Taishido, Setagaya-ku, Tokyo, 154 Japan.
Kimura
H
H
Yamaguchi
A
A
Kamada
N
N
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005434:Flow Cytometry / Q000379:methods; D006084:Graft Rejection / Q000276:immunology*; D006085:Graft Survival / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014184:Transplantation, Homologous / Q000276:immunology