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.
Bibliographical noteFunding Information:
We thank Michelle Larabee for histology. We thank Drs. Kris Hogquist, Rachel Caspi and Jerry Niederkorn for critiques of the manuscript. This work was supported by NIH grant EY11542, Research to Prevent Blindness, the Anna Heilmaier Foundation, and the MN Lions and Lionesses Clubs.
- Immune privilege
- T lymphocytes
- Transgenic mice