title: Resting CD8 T cells recognize beta-galactosidase expressed in the immune-privileged retina and mediate autoimmune disease when activated.
abstract: Although the expression of class II major histocompatibility complex (MHC) in retina is extremely low, it is an established fact that activated CD4 T cells, specific for retinal antigens (Ags), mediate experimental autoimmune uveoretinitis (EAU). Conversely, CD8 T cells have not been shown to recognize Ag in the retina. This study investigated whether retinal-specific Ags are detected by class I MHC-restricted CD8 T cells. Using a CD8 T-cell clone (beta3) specific for an immunodominant epitope of beta-galactosidase (beta-gal), local Ag recognition was shown by transfer of activated beta3 cells into beta-gal transgenic (Tg) mice expressing beta-gal in the retina (hi-arr-beta-gal mice), or in the brain and eye (GFAP-beta-gal mice). Beta-gal-positive photoreceptor cells were damaged in the retina of hi-arr-beta-gal mice, and anterior segment disease was found in the eyes of GFAP-beta-gal mice. Ag recognition by resting CD8 T cells was also evaluated. Recovery of 5(6)-carboxyfluorescein diacetate N-succinimidyl ester (CFSE)-labelled beta3 cells from hi-arr-beta-gal mice was slightly decreased compared to recovery from B10.A mice, while recovery from GFAP-beta-gal mice was transiently increased. Conversely, recovery of CFSE- cells increased in hi-arr-beta-gal mice, consistent with an Ag-dependent response. The CFSE content of the CFSE+ population was unchanged relative to beta3 cells recovered from controls. Intracellular cytokine responses of beta3 cells recovered from hi-arr-beta-gal and GFAP-beta-gal mice correlated with the number of cells recovered, regardless of CFSE content. Even though their production of interferon-gamma and tumour necrosis factor-alpha was affected little by transfer into hi-arr-beta-gal recipients, the ability of beta3 cells to mediate delayed-type hypersensitivity was inhibited in hi-arr-beta-gal mice. These results show that resting CD8 T cells are affected by the presence of Ag that originates in retina and, when activated prior to transfer, mediate pathogenic autoimmunity against retinal and other ocular targets.
authors: Department of Ophthalmology, University of Minnesota, Minneapolis, MN 55455, USA.
authors: Scott W
authors: SW
authors: McPherson
authors: Jing
authors: J
authors: Yang
authors: Chi-Chao
authors: CC
authors: Chan
authors: Chunzhi
authors: C
authors: Dou
authors: Dale S
authors: DS
authors: Gregerson
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D017209:Apoptosis / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D007108:Immune Tolerance; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D012160:Retina / Q000201:enzymology / Q000276:immunology*; D012173:Retinitis / Q000276:immunology*; D001616:beta-Galactosidase / Q000276:immunology* / Q000378:metabolism
chemical_list: D001616:beta-Galactosidase