INTERFERON SYSTEM IN CELLULAR FUNCTION AND DISEASE

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Cytokines, such as interferon (IFN)-gamma and interleukin (IL)-2, are a group of specialized hormone-like proteins that exert profound influences on cellular development and on a variety of cellular functions. This proje has concentrated on studying the ways in which cytokines interact with cells of the immune system and with cells in the ocular microenvironment. We have shown that IFN-gamma and IL-2 are found within the inflamed eye in association with T-cell infiltration and major histocompatibility comple (MHC) class II antigen expression on infiltrating cells and on retinal pigm t epithelial (RPE) cells. Furthermore, IFN-gamma-activated RPE cells can process and present antigens to helper T lymphocytes. Experimentally we demonstrated that isolated human RPE cells can be induced to produce another lymphokine, IL-6, and soluble intercellular adhesion molecule-1 (ICAM-1) following incubation with IFN-gamma. IL-6 is a potent inflammatory cytokine capable of enhancing antibody production and cytotoxic T-cell activities. ICAM-1 is an adhesion molecule that media s cell adhesion, an essential component for several immunologic functions. These studies indicate that cytokine-mediated activation of RPE cells may b a basic component of ocular immunity and an important aspect of RPE cell transplantation. These observations indicate that IFN-gamma induces MHC class I, class II antigen and ICAM-1 expression and IL-6 secretion by RPE cells. All of thes factors may serve as a local amplification system in autoimmune and inflammatory eye disease. A better understanding of the role of cytokines in the mechanisms involved in the development of autoimmunity and inflammation may be beneficial in developing treatments for these diseases.