Retinal antigen-specific T cells mediate experimental autoimmune uveoretinitis (EAU) in PVG rat a model for tracking antigen-specific CD4+T cells in the inflamed eye

Abstract

Experimental autoimmune uveoretinitis (EAU) is a CD(4)(+) T cell mediated organ-specific model of autoimmune disease and is considered a good model of posterior uveitis in man. Previously it has been shown that EAU may be induced in Lewis rats by adoptive transfer of small numbers of retinal antigen-specific CD(4)(+) T cell lines where recruitment of naive T cells is integral to the pathogenesis of uveitis. In order to assess the role of antigen-specific CD(4)(+) T cells in EAU, a model of passively induced EAU has been developed in which retinal extract-specific T cell lines were generated from lymph nodes of immunised PVG-RT(7)(b) rats and maintained with alternating cycles of stimulation with retinal extract presented on syngeneic accessory cells and proliferation in IL-2 rich media. The antigen-specific cell line can be categorised phenotypically by the CD(4)(+) IL-2R(+) OX(42)-OX8- cell surface expression. All cells expressed on their cell surface RT7.2 allotype of CD(45) antigen specific for PVG-RT(7)(b) strain, so that when EAU was induced by adoptive transfer with as little as 5X10(6) cells to PVG-RT(7)(a) recipients, antigen-specific cells of donor allotype (CD(4)(+) RT(7.2)(+)) may be tracked in the recipient (RT(7.1)(+) allotype). This preliminary report describes the isolation of antigen-specific (donor) T cells from the retina in early stages of passively-induced EAU, a model which can now be adopted to investigate the role different populations of cells play in the pathogenesis of EAU.