Resting CD8 T cells recognize β-galactosidase expressed in the immune-privileged retina and mediate autoimmune disease when activated

Scott W. Mcpherson, Jing Yang, Chi Chao Chan, Chunzhi Dou, Dale S. Gregerson

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

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 (β3) specific for an immunodominant epitope of β-galactosidase (β-gal), local Ag recognition was shown by transfer of activated β3 cells into β-gal transgenic (Tg) mice expressing β-gal in the retina (hi-arr-β-gal mice), or in the brain and eye (GFAP-β-gal mice), β-gal-positive photoreceptor cells were damaged in the retina of hi-arr-β-gal mice, and anterior segment disease was found in the eyes of GFAP-β-gal mice. Ag recognition by resting CD8 T cells was also evaluated. Recovery of 5(6)-carboxyfluorescein diacetate N-succinimidyl ester (CFSE)-labelled β3 cells from hi-arr-β-gal mice was slightly decreased compared to recovery from B10.A mice, while recovery from GFAP-β-gal mice was transiently increased. Conversely, recovery of CFSE- cells increased in hi-arr-β-gal mice, consistent with an Ag-dependent response. The CFSE content of the CFSE+ population was unchanged relative to β3 cells recovered from controls. Intracellular cytokine responses of β3 cells recovered from hi-arr-β-gal and GFAP-β-gal mice correlated with the number of cells recovered, regardless of CFSE content. Even though their production of Interferon-γ and tumour necrosis factor-α was affected little by transfer into hi-arr-β-gal recipients, the ability of β3 cells to mediate delayed-type hypersesitivity was inhibited in hi-arr-β-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.

Original languageEnglish (US)
Pages (from-to)386-396
Number of pages11
JournalImmunology
Volume110
Issue number3
DOIs
StatePublished - Nov 2003

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