Treatment with the humanized CD154-specific monoclonal antibody, hu5C8, prevents acute rejection of primary skin allografts in nonhuman primates

Background. Allogeneic skin transplantation remains a rigorous test of any immune intervention designed to prevent allograft rejection. To date, no si ngle, clinically available immunosuppressant has been reported to induce lo ng-term primary skin allograft survival in primates. We have previously sho wn that treatment with the humanized CD154-specific monoclonal antibody, hu manized 5C8 (hu5C8), induces long-term renal allograft survival in nonhuman primates. In this study, we evaluated the efficacy of hu5C8 in preventing primary skin allograft rejection in rhesus monkeys. Methods. Ten rhesus monkeys were transplanted with full-thickness skin allo grafts mismatched at both class I and class II major histocompatibility loc i. Of these, two were given no treatment, five were treated with hu5C8 alon e, and three received hu5C8 combined with whole blood donor-specific transf usion (DST). All recipients also received skin autografts for comparison. A nimals were followed by inspection, serial biopsy, mixed lymphocyte culture , and alloantibody determination. Results. Treatment with hu5C8 alone or hu5C8 plus DST greatly prolonged all ograft survival. Rejection occurred in the untreated group within 7 days. M ean allograft survival in the monotherapy hu5C8 group was > 236 days and in the DST group was > 202 days; these differences were not significant. Reje ction eventually occurred in most animals. Allograft survival was not corre lated with the development of T cell hyporesponsiveness in mixed lymphocyte culture. Rejection was not predicted by the development of donor-specific alloantibody. Conclusion. These results show that treatment with the CD154-specific monoc lonal antibody, hu5C8, greatly delays the onset of acute skin allograft rej ection.