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


CONCLUSIONS
These results demonstrate that retinal expression of very small amounts of a tissue-specific Ag can generate T(reg) in the periphery.
Gregerson
Dale S
DS
Department of Ophthalmology, University of Minnesota, Minnesota, MN 55455-3007, USA. grege001@umn.edu
Heuss
Neal D
ND
Lehmann
Ute
U
McPherson
Scott W
SW
D019264:Adoptive Transfer; D000818:Animals; D017209:Apoptosis / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D007108:Immune Tolerance; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D020419:Photoreceptor Cells, Vertebrate / Q000201:enzymology*; D012160:Retina / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D012173:Retinitis / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000276:immunology / Q000378:metabolism; D015866:Uveitis, Posterior / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D001616:beta-Galactosidase / Q000096:biosynthesis*
D001324:Autoantigens; D001616:beta-Galactosidase