Background: 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.
Methods: 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.
Results: 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).
Conclusion: 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.