CYCLOSPORIN A SPARES SELECTIVELY LYMPHOCYTES WITH DONOR-SPECIFIC SUPPRESSOR CHARACTERISTICS

Abstract

The effect of cyclosporin A (Cy A) on the host responses to heart allografts was examined in rats following administration of the drug for 7 days after grafting. All grafts functioned > 100 days without rejection episodes in animals of major histocompatibility differences. Thymic or splenic lymphocytes (1 .times. 108) from LEW recipients of (LEW .times. BN)F1 hearts were transferred at varying periods into untreated LEW rats transplanted with (LEW .times. BN)F1 test hearts 24 h later. Test grafts survived 12-16 days significantly (P <0.001) longer than in untreated animals (MST [median survival time] .+-. SD = 7 .+-. 0.3 days). Cells from normal LEW animals, Cy A-treated but ungrafted, and grafted but not treated animals, all failed to prolong test graft survival. Specificity of the effect was tested in vivo, using hearts from donor and 3rd-party rats, and in vitro, using the mixed lymphocyte response (MLR). In vivo, thymocytes from treated LEW recipients of (LEW .times. WF)F1 grafts failed to prolong (LEW .times. BN)F1 test grafts; conversely, transferred thymocytes from LEW recipients of (LEW .times. BN)F1 grafts failed to prolong (LEW .times. WF)F1 grafts. The MLR of lymphocytes from Cy A-treated rats was significantly decreased against donor lymphocytes but not against 3rd-party lymphocytes. Cellular and humoral immunity mounted by Cy A-treated recipients was depressed throughout the entire follow-up period. Prolonged heart graft survival after 7 days of Cy A treatment suggests emergence of cells with specific suppressor activity, which in turn may cause profound abrogation of host effector responses against vascularized organ allografts.