Class II antigens are integral glycoproteins encoded by genes in the major histocompatibility complex. Their expression is critical to immune reactivity. Although most immune cells constitutively express class II antigens, some nonimmune cell types can be induced to demonstrate these molecules under selected conditions, such as an immunologic or degenerative event. Based on our earlier data, demonstrating that retinitis pigmentosa patients had an alteration in IFN-gamma production and class II antigen expression, we expanded our studies to evaluate class II antigen expression in a variety of ocular situations. We found that the retinal pigment epithelium (RPE) cell did not express class II antigen in the normal eye. In contrast, the RPE cell did express these molecules in a retinal degenerative disorder (retinitis pigmentosa) and in two ocular inflammatory diseases (sympathetic ophthalmia and uveitis). Using the experimental autoimmune uveitis (EAU) animal model of ocular autoimmune disease, we demonstrated that the RPE cell is activated to express class II antigens prior to clinical and histopathological evidence of the disease. Finally, we demonstrated that EAU could be altered with anti-Ia therapy. In this study, EAU animals receiving monoclonal anti-Ia antibodies experience not only less ocular inflammation but also a delay in the onset of EAU. Moreover, immunocytochemistry analysis revealed that eyes from these animals expressed less Ia antigen as well as a diminution of infiltrating macrophages and lymphocytes. These data show that anti-Ia treatment significantly modifies the course of EAU in the rat. We have also demonstrated that direct inoculation of recombinant IFN-gamma results in the expression of MHC class II (Ia) in a variety of ocular cells. We are continuing to investigate the effects of other potent modulators with the hope that an alteration in activation or expression of these molecules may modify the disease process to the benefit of the host.
