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

• Published in: Investigative ophthalmology & visual science Vol. 48; no. 9; pp. 4153 - 4161
• Main Authors: Peng, Yong, Han, Gencheng, Shao, Hui, Wang, Yali, Kaplan, Henry J, Sun, Deming
• Format: Journal Article
• Language: English
• Published: Rockville, MD ARVO 01.09.2007; Association for Research in Vision and Ophtalmology
• Subjects: Adoptive Transfer; Animals; Autoimmune Diseases - immunology; Autoimmune Diseases - pathology; Biological and medical sciences; Bone Marrow Cells; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - immunology; Cells, Cultured; Dendritic Cells - physiology; Disease Models, Animal; Eye and associated structures. Visual pathways and centers. Vision; Eye Proteins - immunology; Female; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Interferon-gamma - metabolism; Interleukin-17 - metabolism; Ligands; Medical sciences; Mice; Mice, Inbred C57BL; Ophthalmology; Retinol-Binding Proteins - immunology; Specific Pathogen-Free Organisms; Uvea diseases; Uveitis - immunology; Uveitis - pathology; Vertebrates: nervous system and sense organs; Autoimmunity; Enzyme; Transferases; Retinoid; Uvea disease; Experimental study; Characterization; Binding protein; Eye disease; T-Lymphocyte; Uveitis; Ophthalmology; Aminomethyltransferase
• ISSN: 0146-0404; 1552-5783; 1552-5783
• DOI: 10.1167/iovs.07-0251

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). 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. 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. 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.