OCULAR PRODUCTION OF INTERFERON-GAMMA AND LACK OF MAJOR HISTOCOMPATIBILITY COMPLEX-MOLECULES INDUCE IMMUNOLOGICAL CHANGES IN THE INTRAOCULAR ENVIRONMENT

The intraocular immune privilege includes the absence of delayed-type hypersensitivity (DTH) to intraocularly presented antigens. To study t he role of major histocompatibility complex (MHC) molecules in relatio n to the activity of the proinflammatory cytokine interferon-gamma (IF N-gamma) in the maintenance of the intraocular immune privilege, we te sted DTH to intraocularly presented antigens in MHC class I- or class II-deficient mice and in transgenic mice with production of IFN-gamma in the retina (rho-gamma). MHC class I- and class II-deficient mice an d rho gamma mice with or without additional MHC deficiency developed h ypersensitivity to intraocularly presented antigens and increased ocul ar pathology, whereas control animals did not. The abrogation of the i ntraocular immune privilege by IFN-gamma was independent of MHC expres sion and was probably due to disturbance of the blood-retina barrier. The sole lack of MHC class I or class II expression produced similar e ffects, confirming the importance of IFN-gamma and MHC molecules for t he development of uveitis.