Suppressor cells and intrathymic inoculation of donor alloantigens in cardiac transplantation

Abstract

Donor-specific tolerance to a rat heterotopic cardiac allograft has been achieved by the pretransplantation intrathymic injection of donor splenocytes and a single intraperitoneal injection of antilymphocyte serum (ALS). Permanent tolerance is achieved without subsequent immunosuppression therapy. This study investigated the mechanisms responsible for maintenance of the tolerant state. Tolerance was produced in Lewis rats by the administration of 1 mL of ALS intraperitoneally and 5 x 10(7) Lewis Brown Norway (LBN) splenocytes intrathymically 21 days before heterotopic transplantation using an LBN donor. In tolerant Lewis rats bearing LBN allografts for more than 100 days, rejection could not be produced by the intravenous injection of naive Lewis spleen cells (5 x 10(7) cells x 1 day, n = 5; 5 x 10(7) cells x 3 days, n = 5) or cells from Lewis rats sensitized to LBN tissues (5 x 10(7) cells x 3 days, n = 5). Naive Lewis recipients were pretreated with ALS and 6 days later with intravenous spleen cells (25 x 10(7), n = 5) or lymphoid cells (10 to 15 x 10(7), n = 5) from a tolerant animal bearing a viable LBN graft. When transplantation with an LBN donor was done the next day, significant prolongation of LBN allograft survival (mean survival time 32.8 days, p < 0.01; and 22.2 days, p < 0.01; respectively) was seen. Wistar-Furth allograft survival was not prolonged by treatment with ALS and intravenous spleen (n = 5) or lymph node (n = 5) cells from rats tolerant to LBN tissues (mean survival time 8.6 and 9.2 days, control 9 days; p = not significant). The administration of ALS alone (n = 5) did not prolong LBN graft survival (mean survival time 11.8 days). These data suggest that transferable suppressor cells specific for the donor strain are at least in part responsible for the maintenance of long-term allograft survival after intrathymic pretreatment with allogeneic cells.