SUPPRESSOR CELLS AND INTRATHYMIC INOCULATION OF DONOR ALLOANTIGENS INCARDIAC TRANSPLANTATION

Background. Donor-specific tolerance to a rat heterotopic cardiac allo graft has been achieved by the pretransplantation intrathymic injectio n of donor splenocytes and a single intraperitoneal injection of antil ymphocyte serum (ALS). Permanent tolerance is achieved without subsequ ent 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 intrap eritoneally and 5 x 10(7) Lewis Brown Norway (LBN) splenocytes intrath ymically 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 injectio n 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 tis sues (5 x 10(7) cells x 3 days, n = 5). Naive Lewis recipients were pr etreated 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 tole rant animal bearing a viable LBN graft. When transplantation with an L BN donor was done the next day, significant prolongation of LBN allogr aft 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 n ot prolonged by treatment with ALS and intravenous spleen (n = 5) or l ymph node (n = 5) cells from rats tolerant to LBN tissues (mean surviv al time 8.6 and 9.2 days, control 9 days; p = not significant). The ad ministration of ALS alone (n = 5) did not prolong LBN graft survival ( mean survival time 11.8 days). Conclusion. These data suggest that tra nsferable suppressor cells specific for the donor strain are at least in part responsible for the maintenance of long-term allograft surviva l after intrathymic pretreatment with allogeneic cells.