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

Abstract

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.

• Authors: Dale S Gregerson, Neal D Heuss, Ute Lehmann, Scott W McPherson
• Journal: Ophthalmic research (Ophthalmic Res) Vol. 40 Issue 3-4 Pg. 154-9 ( 2008) ISSN: 1423-0259 [Electronic] Switzerland
• PMID: 18421231 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: 2008 S. Karger AG, Basel.

Chemical References

• Autoantigens
• beta-Galactosidase

Topics

• Adoptive Transfer
• Animals
• Apoptosis (immunology)
• Autoantigens (immunology)
• Autoimmune Diseases (enzymology, immunology, pathology)
• Cells, Cultured
• Disease Models, Animal
• Enzyme-Linked Immunosorbent Assay
• Immune Tolerance
• Lymphocyte Activation (immunology)
• Mice
• Mice, Transgenic
• Photoreceptor Cells, Vertebrate (enzymology)
• Retina (enzymology, immunology, pathology)
• Retinitis (enzymology, immunology, pathology)
• T-Lymphocytes, Regulatory (immunology, metabolism)
• Thymus Gland (immunology, metabolism)
• Uveitis, Posterior (enzymology, immunology, pathology)
• beta-Galactosidase (biosynthesis)