Induction of a distinct CD8 Tnc17 subset by transforming growth factor-β and interleukin-6

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Abstract
Cross-talk between TGF-β and IL-6 has been shown to direct the differentiation of CD4+ cells into 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 noncytotoxic, IL-17-producing cells in MLC. These IL-17-producing CD8+ cells exhibit a unique granzyme B−IFN-γ−IL-10− phenotype. The mRNA level of Th2/T cytotoxic 2 (Tc2) transcription factors GATA3 and Th1/Tc1 transcription factors T-box expressed in T cell (T-bet) as well as its target H2·O-like homeobox (Hlx) is decreased in CD8+ cells from TGF-β- and IL-6-treated MLC. In addition, these CD8+ cells display a marked up-regulation of retinoic acid-related orphan receptor-γt, a key IL-17 transcription factor. These results demonstrate that the existence of an IL-17-producing CD8+ subset belongs to neither the Tc1 nor the Tc2 subset and can be categorized as a T noncytotoxic 17 (Tnc17) subset.
Funding Information
  • NHRI (VC-094-PP-02)
  • Chang Gung Memorial Hospital, Taiwan (CMRP1225, 140041)