1. Evidence for Extrathymic Generation of Regulatory T Cells Specific for a Retinal Antigen
- Author
-
Dale S. Gregerson, Scott W. McPherson, Neal D. Heuss, and Ute Lehmann
- Subjects
Adoptive cell transfer ,Apoptosis ,Enzyme-Linked Immunosorbent Assay ,Mice, Transgenic ,Thymus Gland ,Biology ,Lymphocyte Activation ,Autoantigens ,T-Lymphocytes, Regulatory ,Retina ,Photoreceptor cell ,Autoimmune Diseases ,Immune tolerance ,Mice ,Cellular and Molecular Neuroscience ,Antigen ,Immune Tolerance ,medicine ,Animals ,Cytotoxic T cell ,IL-2 receptor ,Antigen-presenting cell ,Cells, Cultured ,Retinitis ,Peripheral tolerance ,Uveitis, Posterior ,General Medicine ,beta-Galactosidase ,Adoptive Transfer ,eye diseases ,Sensory Systems ,Cell biology ,Disease Models, Animal ,Ophthalmology ,medicine.anatomical_structure ,Immunology ,sense organs ,Photoreceptor Cells, Vertebrate - Abstract
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+ Treg. Several strategies were then used to show that β-gal expressed in the retina supported spontaneous, thymus-independent Treg 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.
- Published
- 2008