INTERFERON SYSTEM IN CELLULAR FUNCTION AND DISEASE

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The interferon (IFN) protein, which can modify a variety of biological activities, is considered one of the body's regulatory proteins. Numerous studies have indicated that the IFNs are potent immunoregulators. During the past year, we have been studying the ways in which IFN proteins interact with cells of the immune system and with cells in the ocular microenvironment. Using immunocytochemical analysis, we have developed a sensitive method of identifying the lymphokines IFN-gamma and interleukin 2 (IL-2) at the site of tissue damage. We have identified these lymphokines in inflammatory eye diseases. The presence of these lymphokines is associated with lymphocyte infiltrate predominantly of T cell origin and with the expression of major histocompatibility complex (MHC) class II antigens on both the infiltrating cells and retinal pigment epithelial (RPE) cells. Experimentally, we have shown that this direct intravitreal inoculation of recombinant rat IFN-gamma results in the expression of MHC Class II antigen (Ia) in a variety of ocular cells. In conjunction with Ia expression, two striking changes were noted: an iritis and infiltrating cells in the inner retinal layers. Both of these phenomena have been observed in certain inflammatory eye diseases. IFN-gamma is known to be a potent regulator of gene expression. We found that IFN-gamma enhances the expression of retinal S-antigen, a specific neuronal cell marker. Preliminary studies indicate this IFN-gamma is acting at the level of transcription. These observations indicate that IFN-gamma induced MHC class II antigen expression may serve as a local amplification system in autoimmune and inflammatory eye disease. A better understanding of the role of lymphokines in the mechanisms involved in the development of autoimmunity and inflammation may be beneficial in developing treatments for these diseases.