Research outlined in this grant application is intended to study two separate methods for inducing organ allograft tolerance. One model is a method for removing cells from the transplanted organ capable of inducing allograft rejection. The second model is an attempt to tolerize the recipient of organ allografts by specifically removing a subpopulation of T helper cells actively involved in induction of allogeneic responsiveness. Both of these models make use of basic research data which suggest that murine T helper cells (bearing the L3T4 differentiation antigens) recognize and respond to MHC Class II molecules (Ia molecules) for induction of organ allograft rejection. By specifically removing the MHC Class II bearing cells from endocrine organs through the use of immunotoxins (monoclonal anti-Ia antibodies conjugated with ricin A chain) or by administering AlphaL3T4 antibodies to rodents, we intend to generate organ allograft tolerance which will allow long-term organ allograft survival in the absence of additional immunosuppression. Both of these models have potential applicability to human transplantation models. The use of anti-Ia immunotoxins most readily lends itself to the concept of endocrine organ allotransplantation whereas the selective specific short-term removal of T helper cells from the recipient might be applicable to any allogeneic organ allograft transplantation model.
