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首页> 外文期刊>Nature immunology >A voltage-gated sodium channel is essential for the positive selection of CD4 + T cells
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A voltage-gated sodium channel is essential for the positive selection of CD4 + T cells

机译：电压门控钠通道对于CD4 + T细胞的阳性选择至关重要

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The sustained entry of Ca 2+ into CD4 + CD8 + double-positive thymocytes is required for positive selection. Here we identified a voltage-gated Na + channel (VGSC) that was essential for positive selection of CD4 + T cells. Pharmacological inhibition of VGSC activity inhibited the sustained Ca 2+ influx induced by positively selecting ligands and the in vitro positive selection of CD4 + but not CD8 + T cells. In vivo short hairpin RNA (shRNA)-mediated knockdown of the gene encoding a regulatory β-subunit of a VGSC specifically inhibited the positive selection of CD4 + T cells. Ectopic expression of VGSC in peripheral AND CD4 + T cells bestowed the ability to respond to a positively selecting ligand, which directly demonstrated that VGSC expression was responsible for the enhanced sensitivity. Thus, active VGSCs in thymocytes provide a mechanism by which a weak positive selection signal can induce the sustained Ca 2+ signals required for CD4 + T cell development.
机译：Ca 2+持续进入CD4 + CD8 +双阳性胸腺细胞对于阳性选择是必需的。在这里，我们确定了电压门控的Na +通道（VGSC），它对于CD4 + T细胞的阳性选择至关重要。 VGSC活性的药理学抑制作用抑制了通过积极选择配体和体外积极选择CD4 +而不是CD8 + T细胞诱导的持续Ca 2+内流。体内短发夹RNA（shRNA）介导的编码VGSC调节性β亚基的基因的敲低特异性抑制CD4 + T细胞的阳性选择。 VGSC在外周和CD4 + T细胞中的异位表达赋予了对阳性选择配体作出反应的能力，这直接表明VGSC表达是敏感性提高的原因。因此，胸腺细胞中的活性VGSC提供了一种机制，通过该机制，弱的阳性选择信号可以诱导CD4 + T细胞发育所需的持续Ca 2+信号。

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