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 β-galactosidase (β-gal) were transferred to transgenic (Tg) mice expressing β-gal in retinal photoreceptor cells, or to ROSA26 mice which express β-gal widely. The survival, phenotype, and responsiveness of transferred 3E9 T cells were unaffected by the presence of retinal β-gal, but altered by recognition of β-gal in the ROSA26 mice. Inoculation or induction of activated T cells with specificity for this epitope produced autoimmune uveoretinitis, showing that the retinal β-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.