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G. Shi, C. A. Cox, B. P. Vistica, E. F. Wawrousek, I. Gery; Phenotype Switching by Inflammation-Inducing Polarized T-Helper (Th)17 Cells, but Not by Th1 Cells. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1991. doi: https://doi.org/.
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Analyses of inflammation-inducing Th cells revealed that a proportion of these cells express both IFN-γ and IL-17, suggesting that certain Th cells may switch their phenotype. The identity of the phenotype switching population has remained unresolved for several years, and here we used a system of transgenic mice we developed to identify this Th population.
Polarized Th1 and Th17 cell lines, expressing hen egg lysozyme (HEL)-specific transgenic T-cell receptor, were generated by repeated activation of naive HEL-specific CD4 cells in the presence of polarizing cocktails. Polarized cells were then transferred into recipient mice expressing HEL in their lens, to induce ocular inflammation. On days 5 and 10 post cell transfer, the phenotype of transferred Th1 and Th17 cells in the recipient eye was determined according to intracellular expression of IFN-γ or IL-17, respectively, using flow cytometry. Phenotypic analysis was also performed in vitro following incubation of polarized Th1 and Th17 cells under the opposite polarizing condition.
Whereas no switching to Th17 was detected in eyes of Th1 recipients, substantial proportions of cells expressing IFN-γ, or both IFN-γ and IL-17 were detected in Th17 recipient eyes. The phenotype switch of Th17 cells increased with time and was attributed to exposure to IL-12, a cytokine that is expressed in the inflamed eyes. Moreover, incubation in vitro with Th1-polarizing cocktail, containing IL-12, converted most Th17 into IFN-γ or IFN-γ/IL-17 expressing cells, but no reciprocal conversion was noted with Th1 cells. Also, Th17 cells incubated in Th1 cocktail expressed T-bet, a transcription factor specific to Th1, but Th1 cells did not express ROR-γt, a transcription factor specific to Th17, following incubation in Th17 cocktail.
Polarized Th1 cells fully retain their phenotype in these experimental systems. In contrast, Th17 may switch phenotype to express IFN-γ or both IFN-γ and IL-17, as well as T-bet, following exposure to IL-12, in vivo and in vitro.
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