IL-17/IFN-γ double producing CD8+ T (Tc17/IFN-γ) cells: A novel cytotoxic T-cell subset converted from Tc17 cells by IL-12

It has been reported that IFN-gamma-producing CD8(+) T (Tc1) cells express cytotoxic molecules such as perforin and granzyme B to exhibit higher cytotoxicity against tumor cells compared with Tc2 cells. However, the critical role of IL-17-producing CD8(+) T (Tc17)-cell subsets in tumor immunity remains unclear. Tc17 cells differentiated from naive CD8(+) T cells did not possess cytotoxic molecules and exhibited no strong cytotoxicity. However, when Tc17 effector cells were further cultured with IL-12, they converted into IFN-gamma-producing Tc17 cells, which mainly consisted of IL-17/IFN-gamma double-producing cells (Tc17/IFN-gamma). IL-12-converted Tc17 cells also acquired cytotoxic function in addition to IFN-gamma producibility. Moreover, they showed strong anti-tumor activity both in vitro and in vivo as well as Tc1 cells. Among four distinct subsets in IL-12-converted Tc17 cell populations, the isolated Tc17/IFN-gamma cells exhibited cytotoxicity as well as IFN-gamma-producing Tc1-like cells. Thus, we first indicate direct evidence that Tc17/IFN-gamma cells, which were plastically converted from non-cytotoxic Tc17 cells by IL-12, exhibited strong anti-tumor activity as well as Tc17 cell-derived Tc1-like cells.