Failure of memory (CD44 high) CD4 T cells to recognize their target antigen in retina.
Activated T cells recognize Ag in the retina, an immune privileged tissue, and may mediate autoimmune disease. In contrast, this report asks if resting, Ag-specific CD4(+) CD44(+) T cells can recognize Ag expressed in the retina. As a probe for Ag, 3E9 T cells specific for an immunodominant epitope of beta-galactosidase (beta-gal) were transferred to transgenic (Tg) mice expressing beta-gal in retinal photoreceptor cells, or to ROSA26 mice which express beta-gal widely. The survival, phenotype, and responsiveness of transferred 3E9 T cells were unaffected by the presence of retinal beta-gal, but altered by recognition of beta-gal in the ROSA26 mice. Inoculation or induction of activated T cells with specificity for this epitope produced autoimmune uveoretinitis, showing that the retinal beta-gal is expressed at immunologically significant levels. We conclude that sequestration provides a substantial barrier to recognition of Ag in quiet retina, and that insufficient Ag leaves the retina for detectable immune recognition outside of the retina.
Gregerson
D S
DS
Department of Ophthalmology, University of Minnesota, Minneapolis, MN 55455, USA. grege001@tc.umn.edu
Xiao
J
J
D000818:Animals; D020274:Autoimmune Diseases of the Nervous System / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D017930:Genes, Reporter / Q000235:genetics / Q000276:immunology; D018960:Hyaluronan Receptors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007111:Immunity, Cellular / Q000235:genetics / Q000276:immunology; D007156:Immunologic Memory / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010786:Photoreceptor Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D012164:Retinal Diseases / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D014162:Transfection; D001616:beta-Galactosidase / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology
D018984:Epitopes, T-Lymphocyte; D018960:Hyaluronan Receptors; D001616:beta-Galactosidase