Strategies of monoclonal antibody therapy that induce permanent tolerance of organ transplants.

Treatment of normal rats with certain monoclonal anti-CD4 antibodies, beginning on the day of grafting, prevents heart graft rejection across a full MHC-haplotype mismatch. Adequate doses of antibody MRC OX-35, which is very potent in vivo, led to the induction of authentic specific tolerance of the transplants. In the very stringent grafting test of transplantation of DA skin to high-responder LOU recipients, adjunctive therapy with cyclosporine, in addition to the anti-CD4 antibodies, is required to induce tolerance. Since tolerance persists indefinitely after a 30-day course of treatment and appears to involve T cell-mediated suppression, this form of treatment is of potential clinical interest.