Phenotype Switching by Inflammation-Inducing Polarized Th17 Cells, but Not by Th1 Cells

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Abstract
Th1 and Th17 cells are characterized by their expression of IFN-γ or IL-17, respectively. The finding of Th cells producing both IL-17 and IFN-γ suggested, however, that certain Th cells may modify their selective cytokine expression. In this study, we examined changes in cytokine expression in an experimental system in which polarized Th1 or Th17 cells specific against hen egg lysozyme induce ocular inflammation in recipient mice expressing hen egg lysozyme in their eyes. Whereas only IFN-γ was expressed in eyes of Th1 recipient mice, substantial proportions of donor cells expressed IFN-γ or both IFN-γ and IL-17 in Th17 recipient eyes. The possibility that nonpolarized cells in Th17 preparations were responsible for expression of IFN-γ or IFN-γ/IL-17 in Th17 recipient eyes was contradicted by the finding that the proportions of such cells were larger in recipients of Th17 preparations with 20–25% nonpolarized cells than in recipients of 35–40% preparations. Moreover, whereas incubation in vitro of Th1 cells with Th17-polarizing mixture had no effect on their phenotype, incubation of Th17 with Th1-polarizing mixture, or in the absence of cytokines, converted most of these cells into IFN-γ or IFN-γ/IL-17-expressing cells. In addition, Th17 incubated with the Th1 mixture expressed T-bet, whereas no ROR-γt was detected in Th1 incubated with Th17 mixture. Thus, polarized Th1 cells retain their phenotype in the tested systems, whereas Th17 may switch to express IFN-γ or IFN-γ/IL-17 following activation in the absence of cytokines, or exposure to certain cytokine milieus at the inflammation site or in culture.