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

Abstract

Analyses of inflammation inducing Th cells revealed that a portion of these cells express both IFN‐γ and IL‐17, suggesting that Th1 and/or Th17 may switch their phenotype. Here, we examined phenotype retention in a system in which polarized Th1 or Th17 cells specific against hen egg lysozyme (HEL) induce ocular inflammation in recipient mice expressing HEL in their eyes. Whereas no switching to Th17 was detected in Th1 recipient eyes, substantial proportions of transferred Th17 expressed IFN‐γ, or both IFN‐γ and IL‐17 in Th17 recipient eyes. The phenotype switch of Th17 cells increased with time and was attributed to exposure to IL‐12 that is expressed in the inflamed eyes. Incubation in vitro with Th1 polarizing cocktail (IL‐2+IL‐12) converted most Th17 into IFN‐γ or IFN‐γ/IL‐17 expressing cells, but no reciprocal conversion was noted with Th1 cells. Furthermore, whereas Th1 cells did not express ROR‐γt following incubation with Th17 polarizing cocktail, Th17 expressed T‐bet following incubation with Th1 cocktail. Thus, polarized Th1 cells fully retain their phenotype, while Th17 switch and express IFN‐γ or both IFN‐γ and IL‐17, as well as T‐bet, following exposure to IL‐12. This study is supported by NEI/NIH intramural program.

Persistence of IL‐2 expressing Th17 cells in healthy humans and experimental autoimmune uveitis

“…Interestingly, the decrease in Th17-DP cell number in cultures containing exogenous IL-2 coincided with a corresponding increase in Foxp3 1 T cells while an increase in Th17-DP cells in a IL-2 low environment (culture without exogenous IL-2) was associated with corresponding diminution in the number of Foxp3 1 T cells (Fig. 4B), suggesting that IL-2 might promote plasticity of T-cell subsets, particularly Th17 cells [22][23][24][25][26].…”

Glucocorticoid-resistant Th17 cells are selectively attenuated by cyclosporine A

“…Murine Th1 and Th17 cultures were cultured, as previously reported (32). Human peripheral CD4 + CCR6 − and CD4 + CCR6 + cells were cultured in IL-2 alone (Th0) or with Th17 polarizing cytokines (Th17).…”

Interleukin-23 and T helper 17-type responses in intestinal inflammation: from cytokines to T-cell plasticity

“…IFN-c). This Th17 phenotype instability was discovered initially using TCR transgenic CD4 + T cells polarized in vitro towards Th17 cells, [83][84][85][86] and more recently with highly purified IL-17A + or IL-17F + populations isolated by cytokine-capture assays 85,87,88 or by cell sorting based on surface expression of reporters (such as Thy-1.1, red fluorescent protein, or enhanced yellow fluorescent protein [eYFP]) that mark cells that have activated the IL-17F 84,89,90 or IL-17A 91 programme. There are some general conclusions regarding Th17 stability that can be drawn from these studies.…”

“…These experiments have revealed that in-vitrogenerated Th17 cells lose their IL-17 expression and start to secrete IFN-c following transfer to T-cell-deficient mice. [83][84][85]89 One of these studies employed the T-cell transfer model and Th17 cells (purified based on Thy1.1 expression marking activation of the IL-17F programme) and showed that some of these cells when recovered from mesenteric lymph nodes of colitic Rag )/) recipients had extinguished IL-17 expression and switched on IFN-c production. 84 In contrast to the Th17 phenotype switch observed in T-cell-deficient recipients, Nurieva et al 89 have reported that Th17 cells maintain their phenotype when given to T-cell-sufficient wild-type mice.…”