Cutting Edge: Spontaneous Development of IL-17-Producing γδ T Cells in the Thymus Occurs via a TGF-β1-Dependent Mechanism

In naive animals, gamma delta T cells are innate sources of IL-17, a potent proinflammatory cytokine mediating bacterial clearance as well as autoimmunity. However, mechanisms underlying the generation of these cells in vivo remain unclear. In this study, we show that TGF-beta 1 plays a key role in the generation of IL-17(+) gamma delta T cells and that it mainly occurs in the thymus particularly during the postnatal period. Interestingly, IL-17(+) gamma delta TCR+ thymocytes were mainly CD44(high)CD25(low) cells, which seem to derive from double-negative 4 gamma delta TCR+ cells that acquired CD44 and IL-17 expression. Our findings identify a novel developmental pathway during which IL-17-competent gamma delta T cells arise in the thymus by a TGF-beta 1-dependent mechanism. The Journal of Immunology, 2010, 184: 1675-1679.