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

Abstract

In naive animals, γδ 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-β1 plays a key role in the generation of IL-17⁺ γδ T cells and that it mainly occurs in the thymus particularly during the postnatal period. Interestingly, IL-17⁺ γδ TCR⁺ thymocytes were mainly CD44^highCD25^low cells, which seem to derive from double-negative 4 γδ TCR⁺ cells that acquired CD44 and IL-17 expression. Our findings identify a novel developmental pathway during which IL-17–competent γδ T cells arise in the thymus by a TGF-β1–dependent mechanism.