TY - JOUR
T1 - Resting CD8 T cells recognize β-galactosidase expressed in the immune-privileged retina and mediate autoimmune disease when activated
AU - Mcpherson, Scott W.
AU - Yang, Jing
AU - Chan, Chi Chao
AU - Dou, Chunzhi
AU - Gregerson, Dale S.
PY - 2003/11
Y1 - 2003/11
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=0242491044&partnerID=8YFLogxK
U2 - 10.1046/j.1365-2567.2003.01750.x
DO - 10.1046/j.1365-2567.2003.01750.x
M3 - Article
C2 - 14632667
AN - SCOPUS:0242491044
SN - 0019-2805
VL - 110
SP - 386
EP - 396
JO - Immunology
JF - Immunology
IS - 3
ER -