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Characterization of IL-17+ interphotoreceptor retinoid-binding protein-specific T cells in experimental autoimmune uveitis.
- Source :
-
Investigative ophthalmology & visual science [Invest Ophthalmol Vis Sci] 2007 Sep; Vol. 48 (9), pp. 4153-61. - Publication Year :
- 2007
-
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).<br />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.<br />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.<br />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.
- Subjects :
- Adoptive Transfer
Animals
Autoimmune Diseases pathology
Bone Marrow Cells
Cells, Cultured
Dendritic Cells physiology
Disease Models, Animal
Female
Flow Cytometry
Interferon-gamma metabolism
Ligands
Mice
Mice, Inbred C57BL
Specific Pathogen-Free Organisms
Uveitis pathology
Autoimmune Diseases immunology
CD4-Positive T-Lymphocytes immunology
CD8-Positive T-Lymphocytes immunology
Eye Proteins immunology
Interleukin-17 metabolism
Retinol-Binding Proteins immunology
Uveitis immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0146-0404
- Volume :
- 48
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Investigative ophthalmology & visual science
- Publication Type :
- Academic Journal
- Accession number :
- 17724201
- Full Text :
- https://doi.org/10.1167/iovs.07-0251