Tuning of antigen sensitivity by T cell receptor-dependent negative feedback controls T cell effector function in inflamed tissues.
Tuning of antigen sensitivity by T cell receptor-dependent negative feedback controls T cell effector function in inflamed tissues.
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DOI：
10.1016/j.immuni.2013.11.017
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发表时间：
2014-02-20
期刊：
影响因子：
32.4
通讯作者：
Germain RN
中科院分区：
文献类型：
--
作者：
Honda T;Egen JG;Lämmermann T;Kastenmüller W;Torabi-Parizi P;Germain RN
活化的T细胞必须介导足以清除病原体的效应反应，同时避免过度的组织损伤。在这里，我们结合了动态活体显微镜与T细胞细胞因子反应的离体评估，以生成皮肤中CD 4 + T细胞效应子调节的详细时空图。在对抗原的应答中，效应T细胞在抗原呈递细胞上短暂地停滞，短暂地产生细胞因子，然后恢复迁移。抗原识别导致PD-1上调T细胞的程序性死亡-1（PD-1）糖蛋白，并阻断其典型配体程序性死亡配体1（PD-L1），延长了迁移停滞和细胞因子产生的持续时间，表明PD-1与PD-L1的相互作用是抗原反应性的主要负反馈调节因子。我们推测，免疫系统采用一种机制，涉及T细胞的招聘，短暂的激活和快速脱敏，使T细胞反应迅速调整抗原呈递的变化，并尽量减少对宿主的附带损伤。
Activated T cells must mediate effector responses sufficient to clear pathogens while avoiding excessive tissue damage. Here we have combined dynamic intravital microscopy with ex vivo assessments of T cell cytokine responses to generate a detailed spatiotemporal picture of CD4+ T cell effector regulation in the skin. In response to antigen, effector T cells arrested transiently on antigen presenting cells, briefly producing cytokine and then resuming migration. Antigen recognition led to PD-1 upregulation of the programmed death-1 (PD-1) glycoprotein by T cells and blocking its canonical ligand, programmed death-ligand 1 (PD-L1), lengthened the duration of migration arrest and cytokine production, showing that PD-1 interaction with PD-L1 is a major negative feedback regulator of antigen responsiveness. We speculate that the immune system employs a mechanism involving T cell recruitment, transient activation, and rapid desensitization, allowing the T cell response to rapidly adjust to changes in antigen presentation and minimize collateral injury to the host.