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Updated: Jul 5, 2026

Generation of Induced Regulatory T Cells from Primary Human Naïve and Memory T Cells
Published on: April 16, 2012
Evidence for extrathymic generation of regulatory T cells specific for a retinal antigen
Dale S Gregerson1, Neal D Heuss, Ute Lehmann
1Department of Ophthalmology, University of Minnesota, Minnesota, MN 55455-3007, USA. grege001@umn.edu
Background:
Thymic expression of a photoreceptor cell antigen, interphotoreceptor retinoid-binding protein, is known to generate regulatory T cells (T(reg)) 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 T(reg) is uncertain.
Methods:
Transgenic mice that express beta-galactosidase (beta-gal) in photoreceptor cells, together with beta-gal-specific T cell receptor transgenic mice, were used to study the induction of T(reg) in vivo.
Results:
Transgenic expression of beta-gal on the arrestin promoter led to a spontaneous immunoregulatory response that inhibited the development of immune responses to beta-gal. The regulation was transferred by CD3+4+25+ T(reg). Several strategies were then used to show that beta-gal expressed in the retina supported spontaneous, thymus-independent T(reg) development. The endogenous T(reg) also differed from the T(reg) 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 T(reg) in the periphery.
