Therapy with monoclonal antibodies to CD4: potential not appreciated?

The assumption that CD8+-cytotoxic cells effect graft rejection has diverted many in clinical and experimental transplantation into ignoring the tremendous potential of anti-CD4 monoclonal antibodies as immunosuppressive therapy. Experimental studies over the past several years has shown that anti-CD4 monoclonal antibodies have effects on prolonging graft survival equal to or greater than those of cyclosporine. This therapy has the unique capacity to induce tolerance to the monoclonal antibody itself, thus preventing the production both of antiidiotypic and antimouse immunoglobulin antibodies. Further, many animals develop tolerance to other antigens, including grafted tissue, raising the potential of eliminating the need for long-term immunosuppression. Synergy between anti-CD4 monoclonal antibodies and other immunosuppressives, including anti-CD8 antibodies and cyclosporine, has also been demonstrated. Continued investigation to determine the best monoclonal antibody to use in humans with respect to its epitope, immunoglobulin subclass, and capacity to deplete CD4+ cells is required to maximize the potential of this therapy before clinical trial.