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S.W. McPherson, N.D. Heuss, D.S. Gregerson; CD8 T Cells Specific for Beta–Galactosidase Transfer EAU in Transgenic Recipients that Express Antigen in the Eye and/or Brain . Invest. Ophthalmol. Vis. Sci. 2004;45(13):544.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Models of experimental autoimmune uveoretinitis (EAU) that have been developed to date are based on immunorecognition of antigens in the retinal photoreceptor cell layer by CD4 T cells. The pathology appears to be based on the exuberant, local expression of DTH–like activity based on recognition of Ag on antigen presenting cells, whether local or recruited. Photoreceptor cells are lost, even though they are MHC class II negative. EAU induced by CD8 T cells would be dependent on recognition of antigen in MHC class I, which is more widely expressed in the retina than class II. We asked if CD8 T cells specific for an antigen expressed in photoreceptor cells or astrocytes could mediate EAU. Methods: Lines of CD8 T cells were made from normal B10.A mice vaccinated with a live, recombinant vaccinia virus expressing beta–galactosidase (b–gal). Spleen cells were harvested and stimulated with an H–2Ld peptide of beta–gal, leading to generation of CD8 T cells specific for the peptide TPHPARIGL. Lines were activated in vitro prior to transfer to control and b–gal transgenic mice. Recipient mice expressed b–gal on the arrestin promoter (hi–arr–b–gal mice), the GFAP promoter (GFAP–b–gal mice), F1 hybrid mice (hi–arr x GFAP –b–gal mice) or control mice. Results: Sublines of beta–gal specific CD8 T cells were made that were capable of mediating the total destruction of the photoreceptor cell layer in hi–arr–b–gal mice. In GFAP–b–gal mice, the CD8 T cells infiltrated and damaged the ganglion cell layer, inner nuclear layer, and optic nerve, which express beta–gal in astrocytes. The brain was also targeted in these mice, where the cerebellum was particularly targeted and damaged. The nature of the pathology differed substantially from that found with CD4 T cells in that very little inflammatory infiltrate was found in the retina. Relatively few monocytes and fewer PMN's were observed. Conclusions: Expression of beta–galactosidase in photoreceptor cells and astrocytes makes them a target for activated, antigen–specific CD8 T cells. The immunopathology bears little resemblance to that of EAU mediated by CD4 T cells, but is capable of extensive destruction of photoreceptor cells.
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