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Publication : Peripheral induction of tolerance by retinal antigen expression.

First Author  Gregerson DS Year  2009
Journal  J Immunol Volume  183
Issue  2 Pages  814-22
PubMed ID  19542366 Mgi Jnum  J:151508
Mgi Id  MGI:4353962 Doi  10.4049/jimmunol.0803748
Citation  Gregerson DS, et al. (2009) Peripheral induction of tolerance by retinal antigen expression. J Immunol 183(2):814-22
abstractText  The contribution of peripheral expression of tissue-specific CNS Ags to the generation of tolerance is uncertain. To study this question, we examined mice transgenic (Tg) for expression of beta-galactosidase (beta gal) on the retinal photoreceptor cell arrestin promoter, in conjunction with TCR Tg mice producing CD4(+) T cells specific for beta gal (beta galTCR). Several strategies were used to test the hypothesis that betagal expressed in the retina supported thymus-independent tolerance and regulatory T cell development. Retinal expression generated an immunoregulatory response that depressed development of immune responses to beta gal following systemic immunization with beta gal. This regulation was transferable to naive mice by CD3(+)4(+)25(+) T cells from naive retinal beta gal(+) donors. Experiments that removed the beta gal(+) retina by enucleation showed that subsequent development of a regulatory response was lost. Adoptive transfer of CD25(-) beta galTCR T cells into retinal beta gal Tg mice on the Rag(-/-) background led to regulatory activity that limited lymphopenia-induced proliferation of beta galTCR T cells in mice with retinal expression of beta gal and inhibited the ear-swelling assay for delayed type hypersensitivity. These results show that retinal expression of very small amounts of a tissue-specific Ag can generate tolerance that includes regulatory T cells.
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