Specific unresponsiveness to fully allogeneic kidney allografts in rats induced by procarbazine hydrochloride and antilymphocyte serum.
A short course of procarbazine hydrochloride (PCH; 50 mg/kg) and antilymphocyte serum (ALS; 5 ml/kg), administered to Lewis (LEW;RT1(1] rats in the first week following transplantation of Brown Norway (BN;RT1n) kidneys, substantially prolonged allograft survival and induced long-term survival in 62% of the grafts. The two agents acted synergistically, in that neither of them administered alone had much effect. Graft recipients did not produce detectable cytotoxic antibodies and antigen-reactive cells injected i.v. were not diverted to the liver, thus showing that neither antibodies nor immune complexes are likely to mediate the unresponsiveness. Spleen cells from graft-bearing recipients failed to cause graft-versus-host responses (GVHR) in both (LEW X BN)F1 and (LEW X DA)F1 hybrids, but they specifically suppressed the GVHR given by normal syngeneic cells to donor strain (BN) antigens. This suppression was specific because the response against third-party antigens (DA; RT1a) was unaffected. Adoptive transfer of spleen and thymus cells from PCH-ALS-treated LEW rats bearing healthy BN kidneys caused a profound prolongation of BN graft survival in sublethally irradiated LEW recipients. This transfer was specific and mediated by W3/13+ (T) lymphocytes. It is concluded that a limited regimen of PCH and ALS given in the first postoperative week incites the generation of specific suppressor T lymphocytes and that this form of immunosuppression, even without preoperative donor antigen, is an effective way of prolonging kidney allograft survival.
D000818:Animals; D000961:Antilymphocyte Serum / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006085:Graft Survival / Q000187:drug effects; D007108:Immune Tolerance / Q000187:drug effects*; D007668:Kidney / Q000276:immunology; D016030:Kidney Transplantation; D008297:Male; D011344:Procarbazine / Q000276:immunology*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014181:Transplantation Immunology / Q000187:drug effects; D014184:Transplantation, Homologous
D000961:Antilymphocyte Serum; D011344:Procarbazine