Tissue-specific effects of anti-CD4 therapy in induction of allograft unresponsiveness in high and low responder rats.

In these experiments, we studied the role of anti-CD4 (Ox38) monoclonal antibody in the prevention of heart and/or kidney allograft rejection in low (ACI) and high (Lewis) responder rats. In low responder ACI rats, donor-specific tolerance for heart and kidney allografts (individually or in combination) was achieved by pretransplant anti-CD4 therapy. In high responder Lewis rats, anti-CD4 therapy alone (or combined with anti-CD8 (Ox8), thymectomy or total lymphoid irradiation) did not prevent first-set rejection of heart allografts. This difference was correlated with a more profound and longer lasting CD4+ cell depletion in the low responder strain. Anti-CD4 treatment, however, produced tolerance of kidney transplants in high responder rats. Additionally, anti-CD4 treatment induced tolerance to heart (as well as kidney) allografts in Lewis recipients of combined kidney and heart allografts from ACI. The effects of anti-CD4 treatment thus depend upon the recipient responder status as well as the organs transplanted and the order of transplantation.