Hannover Medical School, Institute for Immunology, Hannover, Germany.
Eur J Immunol. 2009 Dec;39(12):3488-97. doi: 10.1002/eji.200939922.
Gammadelta T cells are a potent source of innate IL-17A and IFN-gamma, and they acquire the capacity to produce these cytokines within the thymus. However, the precise stages and required signals that guide this differentiation are unclear. Here we show that the CD24(low) CD44(high) effector gammadelta T cells of the adult thymus are segregated into two lineages by the mutually exclusive expression of CCR6 and NK1.1. Only CCR6+ gammadelta T cells produced IL-17A, while NK1.1+ gammadelta T cells were efficient producers of IFN-gamma but not of IL-17A. Their effector phenotype correlated with loss of CCR9 expression, particularly among the NK1.1+ gammadelta T cells. Accordingly, both gammadelta T-cell subsets were rare in gut-associated lymphoid tissues, but abundant in peripheral lymphoid tissues. There, they provided IL-17A and IFN-gamma in response to TCR-specific and TCR-independent stimuli. IL-12 and IL-18 induced IFN-gamma and IL-23 induced IL-17A production by NK1.1+ or CCR6+ gammadelta T cells, respectively. Importantly, we show that CCR6+ gammadelta T cells are more responsive to TCR stimulation than their NK1.1+ counterparts. In conclusion, our findings support the hypothesis that CCR6+ IL-17A-producing gammadelta T cells derive from less TCR-dependent selection events than IFN-gamma-producing NK1.1+ gammadelta T cells.
γδ T 细胞是先天 IL-17A 和 IFN-γ的有效来源，它们在胸腺内获得产生这些细胞因子的能力。然而，指导这种分化的确切阶段和所需信号尚不清楚。在这里，我们表明成年胸腺中的 CD24(low) CD44(high)效应性 γδ T 细胞通过 CCR6 和 NK1.1 的相互排斥表达而分为两个谱系。只有 CCR6+γδ T 细胞产生 IL-17A，而 NK1.1+γδ T 细胞是 IFN-γ的有效产生者，但不是 IL-17A 的产生者。它们的效应表型与 CCR9 表达的丧失相关，尤其是在 NK1.1+γδ T 细胞中。因此，这两个 γδ T 细胞亚群在肠道相关淋巴组织中都很少见，但在外周淋巴组织中却很丰富。在那里，它们对 TCR 特异性和 TCR 非依赖性刺激做出反应，提供 IL-17A 和 IFN-γ。IL-12 和 IL-18 分别诱导 NK1.1+或 CCR6+γδ T 细胞产生 IFN-γ和 IL-17A，IL-23 诱导 NK1.1+或 CCR6+γδ T 细胞产生 IL-17A。重要的是，我们表明 CCR6+γδ T 细胞对 TCR 刺激的反应性强于其 NK1.1+对应物。总之，我们的研究结果支持这样一种假设，即 CCR6+产生 IL-17A 的 γδ T 细胞来源于比产生 IFN-γ 的 NK1.1+γδ T 细胞更少依赖 TCR 的选择事件。
