Department of Immunology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
J Immunol. 2010 Feb 15;184(4):1675-9. doi: 10.4049/jimmunol.0903539. Epub 2010 Jan 8.
In naive animals, gammadelta 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-beta1 plays a key role in the generation of IL-17(+) gammadelta T cells and that it mainly occurs in the thymus particularly during the postnatal period. Interestingly, IL-17(+) gammadelta TCR(+) thymocytes were mainly CD44(high)CD25(low) cells, which seem to derive from double-negative 4 gammadelta TCR(+) cells that acquired CD44 and IL-17 expression. Our findings identify a novel developmental pathway during which IL-17-competent gammadelta T cells arise in the thymus by a TGF-beta1-dependent mechanism.
在幼稚动物中，γδ T 细胞是白细胞介素 17（IL-17）的先天来源，IL-17 是一种有效的促炎细胞因子，可介导细菌清除和自身免疫。然而，体内产生这些细胞的机制尚不清楚。在这项研究中，我们表明 TGF-β1 在 IL-17（+）γδ T 细胞的产生中起着关键作用，并且主要发生在胸腺中，特别是在出生后时期。有趣的是，IL-17（+）γδ TCR（+）胸腺细胞主要是 CD44（高）CD25（低）细胞，这些细胞似乎来自双阴性 4γδ TCR（+）细胞，后者获得了 CD44 和 IL-17 的表达。我们的发现确定了一种新的发育途径，在此途径中，通过 TGF-β1 依赖性机制，IL-17 有活性的γδ T 细胞在胸腺中产生。
