TCR signal strength controls thymic differentiation of discrete proinflammatory γδ T cell subsets.
TCR signal strength controls thymic differentiation of discrete proinflammatory γδ T cell subsets.
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DOI：
10.1038/ni.3424
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发表时间：
2016-06
影响因子：
30.5
通讯作者：
Silva-Santos B
中科院分区：
文献类型：
--
作者：
Muñoz-Ruiz M;Ribot JC;Grosso AR;Gonçalves-Sousa N;Pamplona A;Pennington DJ;Regueiro JR;Fernández-Malavé E;Silva-Santos B
小鼠胸腺产生离散的γδ T细胞亚群，产生干扰素-γ（IFN-γ）或白细胞介素17（IL-17），但TCR在此发育过程中的作用仍有争议。在这里，我们表明，小鼠单倍不足的Cd 3g和Cd 3d（CD 3DH，为CD 3双单倍不足）有减少的TCR表达和信号强度选择性γδ T细胞。CD 3DH小鼠的αβ胸腺细胞亚群的数量和表型正常，但胎儿Vγ6+（而不是Vγ4+）产生IL-17的γδ T细胞的分化受损，并且在整个个体发育过程中产生IFN-γ的CD 122 + NK 1.1 + γδ T细胞显著减少。成年CD 3DH小鼠表现出外周IFN-γ+ γδ T细胞减少，并对实验性脑型疟疾具有抗性。因此，特定胸腺发育窗内的TCR信号强度是促炎性γδ T细胞亚群的产生及其对病理生理学的影响的主要决定因素。
The murine thymus produces discrete γδ T cell subsets making either interferon-γ (IFN--γ) or interleukin 17 (IL-17), but the role of the TCR in this developmental process remains controversial. Here we show that mice haploinsufficient for both Cd3g and Cd3d (CD3DH, for CD3 double haploinsufficient) have reduced TCR expression and signaling strength selectively on γδ T cells. CD3DH mice had normal numbers and phenotype of αβ thymocyte subsets but impaired differentiation of fetal Vγ6+ (but not Vγ4+) IL-17-producing γδ T cells and a marked depletion of IFN-γ-producing CD122+ NK1.1+ γδ T cells throughout ontogeny. Adult CD3DH mice showed reduced peripheral IFN-γ+ γδ T cells and were resistant to experimental cerebral malaria. Thus, TCR signal strength within specific thymic developmental windows is a major determinant of the generation of proinflammatory γδ T cell subsets and their impact on pathophysiology.