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(Investigative Ophthalmology and Visual Science. 2007;48:4153-4161.)
© 2007 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.07-0251
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Characterization of IL-17+ Interphotoreceptor Retinoid-Binding Protein-Specific T Cells in Experimental Autoimmune Uveitis

Yong Peng,1,2 Gencheng Han,1,2 Hui Shao,1 Yali Wang,1 Henry J. Kaplan,1 and Deming Sun1

1From the Department of Ophthalmology and Visual Sciences, Kentucky Lions Eye Center, University of Louisville, Louisville, Kentucky.

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-ß 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.




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