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This Article Full Text (PDF) All Versions of this Article: jimmunol.0803748v1 183/2/814    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Gregerson, D. S. Articles by McPherson, S. W. PubMed PubMed Citation Articles by Gregerson, D. S. Articles by McPherson, S. W.

Peripheral Induction of Tolerance by Retinal Antigen Expression

Department of Ophthalmology, University of Minnesota, Minneapolis, MN 55455

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 β-galactosidase (βgal) on the retinal photoreceptor cell arrestin promoter, in conjunction with TCR Tg mice producing CD4⁺ T cells specific for βgal (βgalTCR). Several strategies were used to test the hypothesis that βgal 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 βgal following systemic immunization with βgal. This regulation was transferable to naive mice by CD3⁺4⁺25⁺ T cells from naive retinal βgal⁺ donors. Experiments that removed the βgal⁺ retina by enucleation showed that subsequent development of a regulatory response was lost. Adoptive transfer of CD25^– βgalTCR T cells into retinal βgal Tg mice on the Rag^–/– background led to regulatory activity that limited lymphopenia-induced proliferation of βgalTCR T cells in mice with retinal expression of βgal 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.

Address correspondence and reprint requests to Dr. Dale S. Gregerson, Department of Ophthalmology, University of Minnesota, 2001 6th Street Southeast, Minneapolis, MN 55455-3007. E-mail address: grege001{at}umn.edu