TGF-beta together with IL-21 or IL-6 can drive the differentiation of naive CD8+ T cells into IL-17-producing CD8+ T cells. These IL-17-producing CD8+ T cells are termed Tc17 cells. Tc17 cells preserve plasticity under various conditions in vitro and in vivo. IFN-gamma-producing CD8+ T cells are termed Tc1 cells. However, Tc1 cells are considered relatively stable. In the present study, we show that the combination of TGF-beta plus IL-21, but not IL-6, converts Tc1 cells into Tc17 cells; this conversion is associated with elevated RORalpha, RORgammat, and Batf mRNA levels. These results indicate that Tc1 cells are skewed to the Tc17 cell phenotype under TGF-beta plus IL-21-polarizing conditions. Furthermore, IL-6R is expressed on naive, but not activated, CD8+ T cells. In contrast, IL-21R is expressed on both naive and activated CD8+ T cells. Thus, differential expression profiles of IL-6R and IL-21R on naive and activated CD8+ T cells may be one mechanism by which TGF-beta plus IL-21, but not IL-6, can drive activated CD8+ T cells to differentiate into IL-17-producing cells. Taken together, these results provide a novel viewpoint for the plasticity of Tc1 cells.
