Effect of Prolonged Monoclonal Antibody Administration on Cardiac Allograft Survival in the Rat

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Abstract
After heterotopic cardiac transplantation in the rat, monoclonal antibodies (MoAb) specific for rat T-cell subsets were administered until rejection. Across combined major histocompatibility complex (MHC) and non-MHC differences (WF to Lew) and isolated non-MHC differences (WF to Lew. 1W) cardiac allografts were rapidly rejected in unmodified hosts (7.7 .+-. 1.0 days and 12.2 .+-. 0.8 days respectively). Across combined MHC and non-MHC differences, administration of MoAb OX-19 (pan T-cell) on days -1,0, and 1 (where day 0 was the day of transplantation) and alternate days thereafter until rejection significantly prolonged allograft survival (28.5 .+-. 10.2 days, P < 0.01). Administration of MoAb W3/25 (helper T cell) and MoAb OX-39 (interleukin 2 (IL-2) receptor) prolonged allograft survival (11.3 .+-. 2.6 days, P < 0.05 and 13.3 .+-. 2.0 days, P < 0.01 respectively), whereas MoAb OX-8 (cytotoxic/suppressor T cell) administration had no effect on allograft survival. In contrast, across non-MHC differences (WF to Lew.1W) administration of MoAb OX-8 markedly prolonged allograft survival (85, > 100 .times. 3 days) whereas MoAb W3/25 administration had no effect. The effect of MoAb administration on lymphocyte subsets at rejection was assessed by flow cytometry. The relationship between depletion of targeted T-cell subsets and graft survival was variable. Across both combined MHC and non-MHC and isolated non-MHC differences MoAb OX-8 administration resulted in a marked reduction of OX-8+ cells at rejection with no prolongation of graft survival in the former and indefinite graft survival in the latter. In contrast, OX-19 administration resulted in prolonged graft survival but at rejection there were significant numbers of OX-19+ cells present. Administration of MoAb W3/25 failed to affect a significant reduction in W3/25+ cells, but allograft survival was nonetheless prolonged.