IL-6 trans-Signaling-Dependent Rapid Development of Cytotoxic CD8+ T Cell Function
IL-6 trans-Signaling-Dependent Rapid Development of Cytotoxic CD8+ T Cell Function
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DOI：
10.1016/j.celrep.2014.07.008
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发表时间：
2014-09-11
期刊：
影响因子：
8.8
通讯作者：
Knolle, Percy A.
中科院分区：
文献类型：
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作者：
Boettcher, Jan P.;Schanz, Oliver;Knolle, Percy A.
病毒或细胞内细菌感染的免疫控制依赖于使用颗粒酶B(GzmB)清除感染细胞的细胞毒性CD8(+)T细胞。在炎症过程中，成熟的抗原提呈树突状细胞指示淋巴器官内的幼稚T细胞发育成效应性T细胞。在这里，我们报告了一个在18小时内发生的机制上不同的、更快速的效应性T细胞发育过程。在缺乏天然免疫刺激和已知共刺激信号的情况下，效应T细胞功能的快速获得是通过交叉呈递肝窦内皮细胞(LSECs)实现的。相反，白介素6(IL-6)的反式信号是快速诱导CD8(+)T细胞表达GzmB所必需的，也是足够的。这种LSEC刺激的表达GzmB的CD8(+)T细胞进一步对炎性细胞因子做出反应，引起增强和延长的效应功能。我们的发现确定了IL-6反式信号在CD8(+)T细胞中快速产生效应功能中的作用，这可能有助于疫苗接种策略。
Immune control of infections with viruses or intracellular bacteria relies on cytotoxic CD8(+) T cells that use granzyme B (GzmB) for elimination of infected cells. During inflammation, mature antigen-presenting dendritic cells instruct naive T cells within lymphoid organs to develop into effector T cells. Here, we report a mechanistically distinct and more rapid process of effector T cell development occurring within 18 hr. Such rapid acquisition of effector T cell function occurred through cross-presenting liver sinusoidal endothelial cells (LSECs) in the absence of innate immune stimulation and known costimulatory signaling. Rather, interleukin-6 (IL-6) trans-signaling was required and sufficient for rapid induction of GzmB expression in CD8(+) T cells. Such LSEC-stimulated GzmB-expressing CD8(+) T cells further responded to inflammatory cytokines, eliciting increased and protracted effector functions. Our findings identify a role for IL-6 trans-signaling in rapid generation of effector function in CD8(+) T cells that may be beneficial for vaccination strategies.