XCR1+ dendritic cells promote memory CD8+ T cell recall upon secondary infections with Listeria monocytogenes or certain viruses.
XCR1+ dendritic cells promote memory CD8+ T cell recall upon secondary infections with Listeria monocytogenes or certain viruses.
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DOI：
10.1084/jem.20142350
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发表时间：
2016-01-11
期刊：
影响因子：
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通讯作者：
Dalod M
中科院分区：
文献类型：
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作者：
Alexandre YO;Ghilas S;Sanchez C;Le Bon A;Crozat K;Dalod M
Alexandre等人。证明XCR1+DC在记忆CD8+T细胞对李斯特菌、VSV或痘苗病毒感染的反应中起重要作用，而不是CMV。根据感染的不同，强大的记忆性CTL反应需要XCR1+DC和NK细胞或其他产生干扰素-γ的淋巴细胞之间依赖细胞因子和趋化因子的串扰。在肿瘤发展或许多原发感染过程中，原始CD8+T细胞的启动需要XCR1+树突状细胞(DC)的交叉呈递。记忆性CD8+T淋巴细胞(MCTL)的活化阈值低于幼稚细胞。然而，他们的回忆反应是否取决于XCR1+DC尚不清楚。通过使用一种允许荧光跟踪和有条件地耗尽XCR1+DC的新小鼠模型，我们证明了在不同病原体的继发感染过程中，这些细胞对mCTL回忆的不同需求。在单核细胞增多性李斯特氏菌、水泡性口炎病毒或痘苗病毒的二次攻击中，XCR1+DC有助于促进这一功能，但对于小鼠巨细胞病毒来说是必不可少的。我们破译了XCR1+DC在李斯特菌继发感染时如何促进mCTL回忆。通过首次可视化二次免疫应答过程中XCR1+DC、NK细胞和mCTL的体内编排，以及通过体内中和候选分子，我们证明，感染后非常早期，mCTL被NK细胞增强的、IL-12-和CXCL9产生的XCR1+DC激活，并以依赖CXCR3的方式被吸引。因此，根据感染因子的不同，在二次挑战期间强烈回忆mCTL可能需要细胞因子和趋化因子依赖的细胞因子与XCR1+DC和NK细胞的串扰。
Alexandre et al. demonstrate the XCR1+ DCs are instrumental in memory CD8+ T cell responses to Listeria, VSV or vaccinia virus infection, but not CMV. Depending on the infection, robust memory CTL responses require cytokine- and chemokine-dependent cross-talk between XCR1+ DCs and NK cells or other IFN-γ–producing lymphocytes. Naive CD8+ T cell priming during tumor development or many primary infections requires cross-presentation by XCR1+ dendritic cells (DCs). Memory CD8+ T lymphocytes (mCTLs) harbor a lower activation threshold as compared with naive cells. However, whether their recall responses depend on XCR1+ DCs is unknown. By using a new mouse model allowing fluorescent tracking and conditional depletion of XCR1+ DCs, we demonstrate a differential requirement of these cells for mCTL recall during secondary infections by different pathogens. XCR1+ DCs were instrumental to promote this function upon secondary challenges with Listeria monocytogenes, vesicular stomatitis virus, or Vaccinia virus, but dispensable in the case of mouse cytomegalovirus. We deciphered how XCR1+ DCs promote mCTL recall upon secondary infections with Listeria. By visualizing for the first time the in vivo choreography of XCR1+ DCs, NK cells and mCTLs during secondary immune responses, and by neutralizing in vivo candidate molecules, we demonstrate that, very early after infection, mCTLs are activated, and attracted in a CXCR3-dependent manner, by NK cell–boosted, IL-12–, and CXCL9-producing XCR1+ DCs. Hence, depending on the infectious agent, strong recall of mCTLs during secondary challenges can require cytokine- and chemokine-dependent cross-talk with XCR1+ DCs and NK cells.