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HG Yu, N Kim, YS Yu, DS Lee, KH Park, H Chung; Immune Tolerance Induced by Anti-CD4 Antibody in Experimental Autoimmune Anterior Uveitis . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1546.
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Purpose: We investigated the therapeutic potential of anti-CD4 antibody as an anti-inflammatory agent for the experimental autoimmune anterior uveitis that mimics human endogenous uveitis in clinical appearance. Methods: Lewis rats were immunized with melanin-associated antigen and primary uveitis was induced. The rats were treated with anti-CD4 monoclonal antibody (OX-38) or cyclosporine A for a week and then received secondary immunization with the same antigen at 8 weeks after primary immunization. They were treated from the day of primary immunization (early treatment group) or from the day 14 (delayed treatment group) for a week. The clinical and histological grading of the uveitis was done and the effects of anti-CD4 mAb on the inflammatory cell death and the cytokine expression were analyzed using flow cytometry, TUNEL stain and intracellular cytokine staining. Results: The cell death of CD4+ T cells was dependent on the dose of the antibody. The prevention of the primary uveitis paralleled the deletion of CD4+ T cells. The secondary uveitis was suppressed in the eyes treated with lower doses (0.5, 1 mg/kg) of the antibody, even though there was mild degree of intraocular inflammation in the primary uveitis in these groups. However, in the eyes treated with higher doses (10, 20 mg/kg), the severity of secondary uveitis was slightly reduced. The primary and secondary anti-inflammatory effects of the antibody were evident in the early treatment group. In the eyes treated with cyclosporine A, the total period of the intraocular inflammation was increased even though cyclosporine A suppressed inflammation during the treatment period. In the eyes treated with anti-CD4 mAb, IFN-γ producing CD4+ T cells were decreased and IL-10 producing CD4+ T cells were increased. Conclusion: Anti-CD4 mAb could induce long-term anti-inflammatory effect in experimental autoimmune anterior uveitis and changes in cytokine profiles of CD4+ T cells may explain the suppressing effect. These results suggest that anti-CD4 mAb may be useful for the treatment of CD4+ T cell-mediated autoimmune diseases such as endogenous uveitis. Further studies on the mechanism of tolerance induction of anti-CD4 mAb are needed for the clinical application.
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