IL-17 Secreting CD8+ T Cells: Induction, Plasticity and Role in Anti-Tumor Immunity
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CD8+ T cells activated in the presence of IL-6 and TGF-β secrete IL-17, and are known as Tc17 cells. In mice, adoptive T cell immunotherapy for cancer results in tumor regression and long term survival. In previous work, it was shown that efficacy of Tc17 cell adoptive immunotherapy correlates with Tc17 conversion from IL-17 to IFN-γ production (plasticity). In these studies, we sought to understand the factors that determine Tc17 plasticity, the requirements for Tc17 plasticity, and the role of Tc17 plasticity in an effective anti-tumor response. To investigate Tc17 plasticity in vitro, we first sorted Tc17 cells to obtain pure IL-17+IFN-γ- cells. Purified Tc17 cultured with IL-2 or IL-12 resulted in conversion to an IFN-γ secreting phenotype. Correspondingly, IL-2 and IL-12 also increased expression of the T cell transcription factor T-bet. To understand the factors important for Tc17 plasticity in vivo, we adoptively transferred antigen-specific Tc17 cells, then specifically activated them using a modified vaccina virus that expresses their cognate antigen. Tc17 activation in a pro-inflammatory environment resulted in conversion to IFN-γ secretion. In addition, vaccinia infection increased the expression of T-bet in Tc17 cells. Based on our in vitro data, we tested whether IL-2 or IL-12 were required for Tc17 plasticity in vivo, and found that neither were absolutely required. However, Tc17 conversion required the presence of T-bet. Consistent with those results, we found expression of T-bet was absolutely required for Tc17 adoptive immunotherapy in cancer models. Taken together, these data provide new insight into the plasticity of Tc17, which are becoming more prominent in the fields of autoimmunity and tumor immunology.