TOLERANCE INDUCTION AFTER LIVER-TRANSPLAN TATION AND IMMUNOSUPPRESSION WITH MONOCLONAL-ANTIBODIES AGAINST CD25 ANTI CD54

Clinical liver transplantation involves two immunologic problems 1) ch ronic rejection with loss of grafts. 2) Specific side-effects and indu ction of malignant tumors limit conventional immunosuppression. Protoc ols of selective immunosuppression may help to solve these problems. T his experimental trial assessed tolerance after temporary selective im munosuppression in rat liver transplantation. Orthotopic rat liver tra nsplantation (ORLT) was performed in the fully allogeneic DA(RT1a)- LE W(RT11) combination. FK506 or CsA were administered in therapeutic or subtherapeutic doses alone or combined with mab against CD25 (IL-2R) a nd CD54 (ICAM-1) for 14d p. op. Tolerance was assessed by heterotopic heart transplantation. All LEW recipients died after transplantation o f a DA liver without immunosuppression, while, with temporary immunosu ppression by CsA + CD25 + CD54, all with FK 506 + CD25 + CD54 (CsA or FK 506 in subtherapeutic dose) therapy, 80% survived long-term. Contra ry to FK 506 or CsA monotherapy, mab treated recipients developed immu notolerance without any histological rejection. Immunohistologically r ecipients' macrophages replaced Kupffer cells. Donors' lymphocytes per sisted flow-cytometrically in lymphonodes and spleen. With this first presentation of a protocol of selective immunosuppression tolerance af ter liver transplantation can be induced experimentally. The basic mec hanisms seem to be graft adaptation and microchimerism. Clinical trial s are necessary to assess this protocol.