Cytokines, such as interferon-gamma (IFN-gamma) and interleukin 2 (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 project 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-~ and IL-2 are found within the inflamed eye in association with T-cell infiltration and major histocompatibility complex (MHC) class II antigen expression on infiltrating cells and on retinal pigment epithelium (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, following incubation with IFN-gamma. IL-6 is a potent inflammatory cytokine capable of enhancing antibody production and cytotoxic T-cell activities. These studies indicate that cytokine-mediated activation of RPE cells may be a basic component of ocular immunity and an important aspect of RPE cell transplantation. Retinoblastoma cells are an important model for exploring human malignancy and differentiation. Using these cells, we have shown that IFN-gamma can regulate MHC class I genes at both transcriptional and posttranscriptional levels. In addition, this modulation is not associated with downregulation of N-myc oncogene expression. These observations indicate that IFN-gamma-induced MHC class I and II antigen expression 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.
