Effect Of Interferon Gamma On The Onset And Severity Of

National Eye Institute

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Abstract

Interferon-g (IFNg) is a pleiotropic cytokine that has been implicated in immunopathogenic mechanisms of a number of inflammatory diseases of autoimmune or infectious disease etiology. We had previously generated transgenic rats with targeted expression of IFNg to the eye. This transgenic rat model that has been valuable in studying consequences of chronic exposure of ocular cells to IFNg and its role in inflammatory eye diseases. In the fiscal year, we showed that IFNg interferes with signaling pathways in the eye, changing the developmental fate of cells destined to become lens cells and causing retinal degeneration and apoptotic death of ganglion cells. In this fiscal year our focus has been on its proinflammatory effects in the eye, particularly its role in recruitment of inflammatory cells to the eye during uveitis. In addition to its effects on the kinetics of T cells expressing Va/b T cells, we found that recruitment of lymphocytes expressing TCR Vg/d receptors is also accelerated. T cells expressing Vd1, Vd4 and Vd5 are the earliest clonotypes recruited into the retina during experimental autoimmune uveoretinitis (EAU). Interestingly, the temporal recruitment of Vd5+ T cells coincides with that of Vb8+ T cells, hitherto thought to initiate the pathogenic processes in EAU, suggesting that Vd5+ T cells may also contribute to disease induction. During the course of this study, we discovered several new members of the Vg and Vd receptor family and this is the first characterization of Vg/d T cell receptor usage in EAU.