INDUCTION OF DONOR-SPECIFIC UNRESPONSIVENESS TO CARDIAC ALLOGRAFTS IN RATS BY PRETRANSPLANT ANTI-CD4 MONOCLONAL-ANTIBODY THERAPY

In the present report a monoclonal antibody designated OX-38 directed against the rat CD4 molecule was tested for its ability to prolong the survival of heterotopic vascularized rat heart allografts transplanted across major histocompatibility barriers. Fluorescence- activated cell-sorter analysis showed that administration of OX-38 selectively depleted 80-95% of CD4+cells from peripheral blood of treated rats. The immunosuppressive effects of OX-38 in vivo were verified by suppression of an antibody response against OX-38 itself as a heterologous protein immunogen. Recipient rats received OX-38 antibody as a single agent given in pretransplant regimens. Nine of 12 treated rats have maintained heterotopic abdominal heart allografts for >175 days. Control rats that did not receive antibody therapy rejected their grafts within 14 days. Rats that maintained heart allografts for >100 days accepted second donor strain hearts but rejected third-party heart grafts transplanted into the femoral space. Anti-CD4- induced allograft unresponsiveness persisted for at least 90 days following surgical removal of donor tissue and retransplantation of a second donor-matched heart. These results indicated that transient, pretransplant therapy with monoclonal antibodies directed against the CD4+lymphocyte induced specific, long-lasting unresponsiveness to fully MHC-mismatched cardiac allografts in rats without additional immunosuppression. © 1990 by Williams and Wilkins.