Evidence for extrathymic generation of regulatory T cells specific for a retinal antigen

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Background: Thymic expression of a photoreceptor cell antigen, interphotoreceptor retinoid-binding protein, is known to generate regulatory T cells (Treg) that prevent spontaneous autoimmune disease of the retina. However, the contribution of other endogenous, tissue-specific antigens (Ags) expressed in the retina to the generation of Treg is uncertain. Methods: Transgenic mice that express β-galactosidase (β-gal) in photoreceptor cells, together with β-gal-specific T cell receptor transgenic mice, were used to study the induction of Treg in vivo. Results: Transgenic expression of β-gal on the arrestin promoter led to a spontaneous immunoregulatory response that inhibited the development of immune responses to β-gal. The regulation was transferred by CD3+4+25+ T reg. Several strategies were then used to show that β-gal expressed in the retina supported spontaneous, thymus-independent T reg development. The endogenous Treg also differed from the Treg induced by Ag inoculation into the anterior chamber of the eye. Conclusion: These results demonstrate that retinal expression of very small amounts of a tissue-specific Ag can generate Treg in the periphery.

Original languageEnglish (US)
Pages (from-to)154-159
Number of pages6
JournalOphthalmic Research
Issue number3-4
StatePublished - Apr 2008


  • Autoantigen
  • Peripheral tolerance
  • Regulatory T cells
  • Retina
  • Uveoretinitis


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