Cyclosporin A spares selectively lymphocytes with donor-specific suppressor characteristics

The effect of cyclosporin A (Cy A) on the host responses to heart allografts have been examined in rats following administration of the drug for 7 days after grafting. All grafts functioned greater than 100 days without rejection episodes in animals of major histocompatibility differences. Thymic or splenic lymphocytes (1 X 10(8) from LEW recipients of (LEW X BN)F1 hearts were transferred at varying periods into untreated LEW rats transplanted with (LEW X BN)F1 test hearts 24 hr later. Test grafts survived 12 to 16 days significantly (P less than 0.001) longer than in untreated animals (MST +/- 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 third-party rats, and in vitro, using the mixed lymphocyte response (MLR). In vivo, thymocytes from treated LEW recipients of (LEW X WF)F1 grafts failed to prolong (LEW X BN)F1 test grafts; conversely, transferred thymocytes from LEW recipients of LEW X BN)F1 grafts failed to prolong (LEW X WF)F1 grafts. The MLR of lymphocytes from Cy A-treated rats was significantly decreased against donor lymphocytes but not against third-party lymphocytes. Additionally, both 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.