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 restin g, Ag-specific CD4(+) CD44(+) T cells can recognize Ag expressed in the ret ina. 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 whi ch express beta -gal widely. The survival, phenotype, and responsiveness of transferred 3E9 T cells were unaffected by the presence of retinal beta -g al, but altered by recognition of beta -gal in the ROSA26 mice. Inoculation or induction of activated T cells with specificity for this epitope produc ed autoimmune uveoretinitis, showing that the retinal beta -gal is expresse d at immunologically significant levels. We conclude that sequestration pro vides 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. (C) 2001 Elsevier Science B.V. All rights reserved.