IL-2(high) tissue-resident T cells in the human liver: Sentinels for hepatotropic infection.
IL-2(high) tissue-resident T cells in the human liver: Sentinels for hepatotropic infection.
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DOI：
10.1084/jem.20162115
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发表时间：
2017-06-05
期刊：
影响因子：
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通讯作者：
Maini MK
中科院分区：
文献类型：
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作者：
Pallett LJ;Davies J;Colbeck EJ;Robertson F;Hansi N;Easom NJW;Burton AR;Stegmann KA;Schurich A;Swadling L;Gill US;Male V;Luong T;Gander A;Davidson BR;Kennedy PTF;Maini MK
Pallett等人。鉴定健康人肝脏中分隔的组织驻留记忆CD8 T细胞，这些细胞在受控的嗜肝感染中扩张，并能迅速产生抗病毒细胞因子。这一原型可能会为肝脏靶向T细胞免疫疗法的发展提供信息。肝脏提供耐受性免疫利基，被几种高度流行的病原体以及原发和转移性肿瘤所利用。我们对健康的和感染了乙肝病毒(乙肝病毒)的人的肝脏进行了采样，以探索特定的T细胞亚群，这些T细胞专门用于克服局部限制和调节免疫。我们鉴定了在肝脏内发现的T-BetloEomesloBlimp-1hiHobitlo T细胞，而不是表达肝脏归巢/滞留标记(CD69+CD103+CXCR6+CXCR3+)的循环记忆CD8 T细胞池。这些组织驻留的记忆T细胞(TRM)在部分免疫控制乙肝病毒感染的患者中优先扩增，并在感染缓解后保留在肝脏中，包括针对所有主要乙肝病毒蛋白中的表位的分区反应。连续的IL-15或抗原暴露后的转化生长因子β诱导肝适应的TRM，包括它们标志性的耗竭标记PD-1和CD39的高表达。我们认为，这些抑制分子，加上反常的强大、快速、细胞自主的IL-2和干扰素γ的产生，使肝脏CD8TRM在发挥局部非细胞毒性肝脏免疫监视的同时得以生存。
Pallett et al. identify tissue-resident memory CD8 T cells compartmentalized in the healthy human liver that expand in controlled hepatotropic infection and can swiftly produce antiviral cytokines. This prototype may inform the development of liver-targeted T cell immunotherapy. The liver provides a tolerogenic immune niche exploited by several highly prevalent pathogens as well as by primary and metastatic tumors. We have sampled healthy and hepatitis B virus (HBV)–infected human livers to probe for a subset of T cells specialized to overcome local constraints and mediate immunity. We characterize a population of T-betloEomesloBlimp-1hiHobitlo T cells found within the intrahepatic but not the circulating memory CD8 T cell pool expressing liver-homing/retention markers (CD69+CD103+ CXCR6+CXCR3+). These tissue-resident memory T cells (TRM) are preferentially expanded in patients with partial immune control of HBV infection and can remain in the liver after the resolution of infection, including compartmentalized responses against epitopes within all major HBV proteins. Sequential IL-15 or antigen exposure followed by TGFβ induces liver-adapted TRM, including their signature high expression of exhaustion markers PD-1 and CD39. We suggest that these inhibitory molecules, together with paradoxically robust, rapid, cell-autonomous IL-2 and IFNγ production, equip liver CD8 TRM to survive while exerting local noncytolytic hepatic immunosurveillance.