Characterization of IL-17+Interphotoreceptor Retinoid-Binding Protein-Specific T Cells in Experimental Autoimmune Uveitis

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Abstract
Purpose. The aims of this study were to determine whether IL-17+ T cells were present in CD4 and CD8 interphotoreceptor retinoid-binding protein (IRBP)-specific T cells and to determine the role of antigen-specific and nonspecific IL-17+ T cells in the pathogenesis of experimental autoimmune uveitis (EAU). Methods. B6 mice were immunized with uveitogenic peptide IRBP1–20. In vivo-primed T cells were separated and stimulated with the immunizing peptide. Intracellular expression of IFN-γ and IL-17 by the T cells was assessed, and the pathogenic activity of the activated T cells was determined. Results. A subset of autoreactive IRBP-specific CD8 T cells expressed IL-17. IRBP-specific T cells preferentially expressed IL-17 when expanded by IL-23, whereas IFN-γ–expressing cells were dominant when the T cells were cultured with IL-2. Importantly, both expanded T-cell populations were uveitogenic. In addition, IL-23 promoted the expansion of antigen-specific and non–antigen-specific IL-17+ T cells, whereas TGF-β and IL-6 acted only on non–antigen-specific IL-17+ T cells. Only the antigen-specific IL-17+ T cells were uveitogenic. The activation of autoreactive IL-17+ T cells was markedly increased in vivo by the mycobacterial component of CFA and pertussis toxin (PTX) and in vitro by the ligation of Toll-like receptors. Conclusions. IL-17+ T cells can be readily detected among activated autoreactive and bystander T cells and may play a major role in the pathogenesis of EAU.