Cross-talk between TGF-β and IL-6 has been shown to direct the differentiation of CD4+ cells into a special IL-17-secreting cells, which are termed Th17 cells. In this study, we demonstrated that TGF-β and IL-6 could stimulate CD8+ cells to differentiate into non-cytotoxic IL-17-producing cells in mixed lymphocyte culture (MLC). These IL-17- producing CD8+ cells exhibit a unique granzyme B−IFN-γ−IL-10− phenotype. The mRNA level of Th2/Tc2 transcription factors GATA3 and Th1/Tc1 transcription factors T-bet, as well as its target Hlx, are decreased in CD8+ cells from TGF-β and IL-6 treated MLC. In addition, these CD8+ cells display a marked upregulation of orphan nuclear receptor RORγt, a key IL-17 transcription factor. These results demonstrate the existence of an IL-17-producing CD8+ subset belong to neither the Tc1 nor the Tc2 subset, and can be categorized as a Tnc17 subset
