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H. Shao, Y. Bian, H. J. Kaplan, D. Sun; Characterization of Rat Interphotoreceptor Retinoid-Binding Protein (IRBP)-Specific Th1 and Th17 Cells in Monophasic and Recurrent Experimental Autoimmune Uveitis (EAU). Invest. Ophthalmol. Vis. Sci. 2009;50(13):2638.
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© ARVO (1962-2015); The Authors (2016-present)
Emerging evidence supports the notion that the IL-17 producing T cells (Th17 cells) play an important role in the inflammatory response of autoimmune diseases. We wished to determine whether eye-infiltrating autoreactive T cells differ between monophasic and relapsing uveitis, and whether Th1 and Th17 autoreactive T cells play distinctive roles in monophasic versus recurrent uveitis.
Monophasic Uveitis (m-EAU) was induced in Lewis rats by immunization with the uveitogenic IRBP1177-1191 peptide (R16) and the recurrent uveitis (r-EAU) was induced by adoptive transfer of R16 specific T cells. Disease severity was evaluated by microscopy and histology and eye infiltrated cells analyzed by flow cytometry.
Analysis of the cellular components of eye-infiltrating cells revealed that within the inflamed eye of m-EAU, Th17 cells were dominant in the earlier stage, and declined gradually with disease resolution. In contrast; the number of Th1 cells was lower than Th17 cells in the early stages of disease but gradually increased during the peak and remission of eye inflammation. During r-EAU, abundant IFN-γ single positive cells and IFN-γIL-17 double positive T cells were found in the early stage of disease; the double positive cells gradually declined, while the IFN-γ T cells persisted in the entire disease process. Only a few IL-17 single positive T cells were found in the inflamed eye during the entire disease episode. The high percentage of Th17 cells in m-EAU seemed to be induced by Mycobacterium tuberculosis mixed in IFA, since IFA alone induced only Th1 but not Th17 cells. Furthermore, IRBP specific Th1 cells polarized by in vitro IL-12 induced r-EAU.
A change in the ratio of autoreactive T cell subsets between Th17 and Th1 appears to correlate with disease recovery m-EAU. The appearance of IFN-γIL-17 double positive autoreactive T cells may correlate with the acute attack of eye inflammation in r-EAU. The pathogenic and immunoregulatory function of single positive and double positive autoreactive T cells remain to be further investigated.
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