'Coreceptor tuning': cytokine signals transcriptionally tailor CD8 coreceptor expression to the self-specificity of the TCR
'Coreceptor tuning': cytokine signals transcriptionally tailor CD8 coreceptor expression to the self-specificity of the TCR
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DOI：
10.1038/ni1512
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发表时间：
2007-10-01
影响因子：
30.5
通讯作者：
Singer, Alfred
中科院分区：
文献类型：
--
作者：
Park, Jung-Hyun;Adoro, Stanley;Singer, Alfred
T细胞免疫需要T细胞的长期存活，这些T细胞能够识别自身抗原，但不是明显的自身反应。这种平衡是如何实现的，目前尚不完全清楚。在这里，我们确定了一种动态平衡机制，该机制在转录上调整单个CD8+T细胞中CD8辅受体的表达，以适应其克隆型T细胞受体(TCR)的自身特异性。“共受体调节”是细胞因子和TCR信号相互作用的结果，白介素7和其他常见的伽马链细胞因子的信号在转录上增加CD8的表达，从而促进自身配体的TCR参与，而TCR信号则削弱常见的伽马链细胞因子信号，从而降低CD8的表达。这种动态的相互作用诱导单个CD8+T细胞表达适合其TCR自身特异性的CD8，促进自身配体的结合，同时避免自身反应。
T cell immunity requires the long-term survival of T cells that are capable of recognizing self antigens but are not overtly autoreactive. How this balance is achieved remains incompletely understood. Here we identify a homeostatic mechanism that transcriptionally tailors CD8 coreceptor expression in individual CD8+ T cells to the self-specificity of their clonotypic T cell receptor (TCR). 'Coreceptor tuning' results from interplay between cytokine and TCR signals, such that signals from interleukin 7 and other common gamma-chain cytokines transcriptionally increase CD8 expression and thereby promote TCR engagement of self ligands, whereas TCR signals impair common gamma-chain cytokine signaling and thereby decrease CD8 expression. This dynamic interplay induces individual CD8+ T cells to express CD8 in quantities appropriate for the self-specificity of their TCR, promoting the engagement of self ligands, yet avoiding autoreactivity.