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Darren J. Lee, Andrew W. Taylor; Following EAU Recovery There Is an Associated MC5r-Dependent APC Induction of Regulatory Immunity in the Spleen. Invest. Ophthalmol. Vis. Sci. 2011;52(12):8862-8867. doi: 10.1167/iovs.11-8153.
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IRBPp-specific regulatory immunity is found in the spleens of mice recovered from experimental autoimmune uveoretinitis (EAU). Induction of this regulatory immunity is dependent on the expression of the melanocortin 5 receptor (MC5r). Therefore, the authors investigated whether dependence on the expression of MC5r was with the T cells or with the APCs mediating protective regulatory immunity in the EAU-recovered mouse spleen.
Wild-type and MC5r−/− mice were immunized to induce EAU. The IRBPp-stimulated T-cell response in spleens of wild-type and MC5r−/− mice were compared for surface markers and cytokine production. Spleen APC were isolated and used to stimulate cytokine production and regulatory activity in IRBP-specific T cells from wild-type or MC5r−/− mice assayed in culture by ELISA, by flow cytometry, and in vivo by adoptive transfer into EAU mice.
IRBPp-specific CD25+CD4+ T cells from spleens of EAU-recovered wild-type mice express a Treg cell phenotype of FoxP3 and TGF-β compared with the effector T-cell phenotype of IFN-γ and IL-17 production in EAU-recovered MC5r−/− mice. APCs from the spleens of wild-type mice recovering from EAU promoted regulatory T-cell activation in IRBP-specific effector T cells from the spleens of EAU-recovering MC5r−/− mice. Spleen APCs from EAU-recovering wild-type, but not MC5r−/−, mice induced TGF-β expression by primed IRBP-specific effector T cells.
Dependence on MC5r expression is with an APC that promotes or selectively activates IRBP-specific FoxP3+ TGF-β+ CD25+CD4+ Treg cells in the spleens of EAU-recovered mice.
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