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Upon activation, naive CD4(+) T cells differentiate into effector Th cell subsets. The stability and plasticity of effector Th cells have not been well understood. In this study we used an IL-17F-red fluorescent protein reporter mouse to analyze the plasticity of Th17 cells in vitro and in vivo. We found that in vitro generated Th17 cells poorly maintained their differentiation program in vitro and could be reprogrammed into other T cell lineages. Moreover, upon transfer into lymphopenic hosts, Th17 cells rapidly lost their IL-17 expression and were converted into Th1 cells independently of IL-7 signaling. However, Th17 cells maintained their phenotypes well in normal animals, even in the absence of Ag and inflammation. These results, although suggesting the plasticity of Th17 cells, also indicate active maintenance of their program in vivo.

Cutting Edge: In Vitro Generated Th17 Cells Maintain Their Cytokine Expression Program in Normal but Not Lymphopenic Hosts