No abstract

RORγt + T H 17 cells are a proinflammatory CD4 + T-cell population associated with autoimmune tissue injury. In mice, priming of T H 17 requires TGF-β, which alone directs the priming of FOXP3 + regulatory T cells (Treg), in association with inflammatory cytokines. Priming of human T H 17 cells from conventional naive CD4 + T cells under similar conditions, however, has proved difficult to achieve. Here, we report that differentiation of human T H 17 cells preferentially occurs from FOXP3 + naive Treg (NTreg) in the presence of IL-2 and IL-1β and is increased by IL-23 and TGF-β. IL-1β-mediated differentiation correlated with IL-1RI expression in stimulated NTreg and was accompanied by induction of RORγt along with down-regulation of FOXP3. IL-17-secreting cells in NTreg cultures cosecreted TNF-α and IL-2 and contained distinct subpopulations cosecreting or not cosecreting IFN-γ and other T H 17-associated cytokines. Polarized NTreg contained significant subpopulations of CCR6-expressing cells that were highly enriched in IL-17-secreting cells. Finally, analysis of CCR6 expression with respect to that of IL-1RI identified distinct IL-17-secreting subpopulations that had maintained or lost their suppressive functions. Together our results support the concept that priming of human T H 17 from naive CD4 + T cells preferentially takes place from FOXP3 + Treg precursors in the presence of lineage-specific polarizing factors.IL-1 | IL-17 | IL-23 | TGF-β | CD4 T cells

Antitumor type I T-cell responses involving IFN-g production are critical to control cancer, but the efficacy of this response is limited by a variety of immunosuppressive mechanisms that promote tumoral immune escape.