Significance of thymus differential ratio in immunologic status of graft tolerance

LEW with BDE-heart graft received 0 (control), 15, or 40 mg cyclosporine (CsA)/kg b. wt. per day. On postoperative days 3, 5, 7, 10, and 14 in four animals each weight and cell count of thymus and spleen were determined, and thymus and spleen cell subpopulations were examined with monoclonal antibodies. The same tests were performed in FiS heart graft recipients without immunosuppression and ungrafted LEW which received 15 or 40 mg CsA. We expressed alterations in thymocyte subpopulations by using the differentiation ratio (DR), i.e., differentiated in % of all T-cells and by the ratio of helper to suppressor/cytotoxic T-cells (Th-Ts/c). In graft rejection the thymus showed no significant change in DR or Th-Ts/c. However, in the CsA-induced graft tolerance DR was elevated and at the same time Th-Ts/c declined, both showing maximum values on days 5 and 7 and a return to normal thereafter. FiS graft recipients exhibited similar thymus alterations as tolerant recipients, but less marked. In CsA-treated ungrafted LEW, elevation of DR was slight after 15 mg but very strong after 40 mg CsA (93% on day 7), and it did not return to normal in the latter group. Th-Ts/c was decreased in these ungrafted animals, but not as strongly as in tolerant graft recipients. Such thymus alterations were not observed in graft rejection. Spleen weights were strongly increased in graft rejection and unchanged in graft tolerance. Splenic Ts/c and Th-Ts/s were increased in CsA-treated tolerant recipients but not in graft rejection. We conclude that elevation of DR and decline of thymic Th-Ts/c in the initial postoperative phase are indicators of graft tolerance in organ recipients.