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.
Yin
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Department of Medicine, Stanford University School of Medicine, CA 94305-5111, USA.
Fathman
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CG
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015704:CD4 Antigens / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D006085:Graft Survival / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology; D007108:Immune Tolerance; D016030:Kidney Transplantation / Q000276:immunology; D008297:Male; D009928:Organ Specificity / Q000276:immunology; D051381:Rats; D011912:Rats, Inbred ACI; D011917:Rats, Inbred Lew; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; C108170:OX-38 monoclonal antibody