Evaluation of Ia expression in rat ocular tissues following inoculation with interferon-gamma

It is becoming increasingly clear that IFN-gamma is a potent immunoregulatory protein which influences MHC class II (Ia) antigen expression and cellular functions of B cells, T cells, NK cells and macrophages. During the past 5 yr our laboratory has provided evidence that IFN-gamma modulates class II antigens on retinal cells (retinal pigment epithelial cells, endothelial cells) and is localized within the eye during human inflammatory conditions. In this study we evaluate the direct effect of IFN-gamma on ocular tissue. Lewis rats were inoculated intravitreally or under the retina with either recombinant IFN-gamma (20,000 U) or saline. At 2 hr, 1, 2 and 6 days postinoculation, the eyes were removed and frozen sections were evaluated by immunocytochemical staining with monoclonal anti-Ia antibodies and an irrelevant monoclonal anti-T cell antibody. Saline treated tissue and tissue removed 2 hr after IFN-gamma inoculation showed no significant staining for Ia antigens. However, eyes evaluated 24 hr after IFN-gamma inoculation revealed Ia expression on a variety of ocular cells localized in the conjunctiva and anterior segment, such as conjunctival epithelium, keratocytes, iris epithelium, ciliary epithelium and choroidal cells. In the retina, retinal pigment epithelial (RPE) cells were Ia positive only when IFN-gamma was injected directly under the retina. In conjunction with Ia expression, two striking changes were noted. An iritis was seen and infiltrating cells were detected in the inner retinal layers. Both of these phenomena have been observed in certain inflammatory eye diseases. These studies clearly substantiate the concept that IFN-gamma can regulate class II antigens in the eye and thus may perpetuate immune reactivity in this site.