EFFECT OF INTERFERON GAMMA ON THE ONSET AND SEVERITY OF UVEITIS

National Eye Institute

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Abstract

Interferon-g (IFN g) is a pleiotropic cytokine that has been implicated in immunopathogenic mechanisms of a number of inflammatory diseases of autoimmune or infectious disease etiology. However, its exact role is still a matter of debate. In experimental mouse models, IFN g has been shown to exacerbate autoimmune thyroiditis, insulin-dependent diabetes mellitus and autoimmune neuritis while it confers protection against experimental allergic encephalomyelitis and experimental uveitis. In this study, we used transgenic rats with constitutive expression of IFN g in the eye to study its paracrine effects and to investigate whether local production of IFN g affects the efferent immune response to S-Antigen, a retinal protein that induces uveitis in rodents. IFN g was found to induce the expression of ICAM-1, interferon-inducible transcription factors, IRF-1 and ICSBP and predispose the rats to development of severe uveitis. Analysis of TCR Vg/d usage in these rats indicate that IFNg expression also influenced the retinal g/d T cell repertoire during uveitis. Characterization of antigen receptors of T cells recruited into the retina of the wild type and transgenic rat retinas will provide insights into g/d T cell types that may be involved in immunopathogenic mechanisms of uveitis.