Effects of monoclonal antibodies directed at cell surface molecules on murine experimental autoimmune uveoretinitis.

Abstract

To elucidate the immunopathogenic mechanism of endogenous uveitis, the effects of monoclonal antibodies to molecules involved in the immune response were studied in murine experimental autoimmune uveoretinitis (EAU). Monoclonal antibodies to CD4, CD8, Ia(k), Ia(d), lymphocyte function-associated antigen-1 (LFA-1), and intercellular adhesion molecule-1 (ICAM-1) were used in this study. The monoclonal antibodies were added in the culture of lymph node cells from B10.BR mice(H-2(K)) immunized with interphotoreceptor retinoid-binding protein (IRBP) and the inhibition of proliferative response was measured. In vivo, IRBP-immunized mice were treated with a high dose of the antibody, and the EAU induction was examined both clinically and pathologically. Proliferative response of IRBP-sensitized lymph node cells was inhibited strongly by anti-CD4 or anti-LFA-1 monoclonal antibody and moderately by anti-Ia(k) or anti-ICAM-1 monoclonal antibody. In contrast, no inhibitory effect of anti-CD8 or anti-Ia(d) monoclonal antibody was observed. In vivo treatment with anti-CD4 monoclonal antibody inhibited development of EAU in a dose-dependent manner, while in vivo treatment with other monoclonal antibodies did not cause significant suppression of EAU. CD4, Ia, LFA-1, and ICAM-1 molecules play important roles in the antigen-specific immune response of lymphocytes. However, in in vivo treatment with monoclonal antibodies to these molecules, only anti-CD4 monoclonal antibody had a strong inhibitory effect on the development of EAU.