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S.W. McPherson, N. Heuss, D.S. Gregerson; Antigen Presentation is a Limiting Factor in CD8 T Cell Mediated Retinal Autoimmune Disease . Invest. Ophthalmol. Vis. Sci. 2005;46(13):1137.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: The pathogenesis of CD8 T cell mediated autoimmune disease in the retina has only been recently described. The purpose of this study is to assess and compare the local presentation of MHC class I–restricted antigen expressed in photoreceptor cells (PC) and/or astrocytes. Methods: CD8 T cells specific for E. coli beta–galactosidase (b–gal) were made from B10.A mice inoculated with recombinant vaccinia virus expressing b–gal followed by b–gal peptide stimulation of cultured splenocytes. Activated T cells were transferred into control and transgenic (Tg) mice expressing b–gal in retinal PC (hi–arr–b–gal mice), or brain and eye via astrocytes (GFAP–b–gal mice), or F1 hybrid mice. Dendritic cells (DC) purified from B10.A mice were inoculated into the anterior chamber of the eye at the time of T cell transfer to assess local antigen presentation. Results: b–gal–specific CD8 T cells damaged the PC in the hi–arr–b–gal mice. The pathology differed significantly from CD4 T cells induced experimental autoimmune uveoretinitis in that very little inflammatory infiltrate was found in the retina. The retinal immunopathology was significantly enhanced by the addition of exogenous DC. In GFAP–b–gal mice, antigen–specific T cells attacked the retinal astrocytes, optic nerve, and tissues of the anterior segment that expressed b–gal. Astrocytes expressing b–gal in the brain of GFAP–b–gal mice were also a target for the T cells with particular damage to the cerebellar granule layer. In F1 hybrid mice, the immunopathology of the T cell responses in brain versus retina were dissociated in time. The brain was severely affected at early time points while the PC were unaffected despite a much higher concentration of antigen in the retina. Immunopathology in F1 hybrids to the retinal PC was observed 7–10 days after the peak of brain disease. Conclusions: As evidenced by the brain being the preferred site of immunopathology, despite much lower b–gal levels, and the enhancement of retinal PC pathology with the addition of exogenous DC, our results show that MHC class–I antigen presentation is significantly limited in the retina compared to the brain. Thus, limited antigen presentation is a significant contributor to retinal immune privilege.
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