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-gamma 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-gamma-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-beta 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.
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-gamma 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-gamma-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-beta 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.
Authors: E Lubberts; L A Joosten; B Oppers; L van den Bersselaar; C J Coenen-de Roo; J K Kolls; P Schwarzenberger; F A van de Loo; W B van den Berg Journal: J Immunol Date: 2001-07-15 Impact factor: 5.422
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