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S. W. McPherson, N. D. Heuss, D. S. Gregerson; Modulation of CD4+ and CD8+ T Cell Responses by Retinal-Antigen Specific Regulatory T Cells. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3815.
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Previously we demonstrated that retinal antigens (Ags) induce Ag-specific regulatory T cells (Tregs) that modulate immune mediated pathology and delayed type hypersensitivity (DTH). In this study we use several different T cell receptor (TCR) transgenic (Tg) mice to further examine the functional nature of retinal-Ag specific Tregs and their role in maintaining retinal immune privilege.
Class II MHC-restricted (CD4+ T cell) TCR Tg mice on either the B10.A background (bgalTCR mice) or the B6 background (BG2 mice) and a class I MHC-restricted (CD8+ T cell) TCR Tg on the B6 background (BG1 mice), all specific for beta-galactosidase (bgal), were used along with Tg mice expressing bgal in photoreceptor cells (B10.A-arrbgal mice or B6-arrbgal mice). Pathogenicity was assayed by adoptive transfer of TCR Tg T cells or by immunization with bgal. DTH responses were assayed by injection of bgal into the ear pinna.
Protocols that reliably induced retinal autoimmune pathology in arrbgal mice but failed to generate disease in B10.A-arrbgal x bgalTCR double Tg mice also failed to induce disease in B6-arrbgal x BG1 mice suggesting the presence of Tregs generated from the non-TCR Tg T cell in those mice. The inability to induce disease could be overcome by irradiating or by anti-CD25 antibody treatment of recipient mice prior to the disease induction protocol. BG1 mice (CD8+ T cells) could mediate a DTH response to bgal but the response was reduced in B6-arrbgal x BG1 double Tg mice. Enucleated B10.A-arrbgal x bgalTCR x Rag-/- mice had a reduced DTH response compared to enucleated bgalTCR x Rag-/- mice.
These results support our earlier findings that retinal Ags induce a population of retinal-Ag specific Tregs that contributes to retinal immune privilege. Our findings also suggest that the Tregs are generated in the periphery and do not require continuous Ag presence to be functional. Further, our results indicate that CD4+ Tregs can modulate immunopathology and DTH mediated by CD8+ T cells.
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