美国耶鲁大学医学院的Richard Flavell团队、Nicola Gagliani团队联合取得一项新突破。他们的研究开发出了效应器TH17细胞产生长寿命的TRM细胞，这些细胞对细菌感染的即时反应至关重要。 2019年8月22日出版的《细胞》发表了这项成果。
研究者采用IL-17A追踪-命运小鼠模型，发现在用热灭活的肺炎克雷伯氏菌（Kp）免疫后，肺CD4 TRM细胞中有很大一部分来自产生IL-17A的效应细胞(T H17)。这些exTH17 T RM细胞由淋巴管内皮细胞产生的IL-7维持在肺部。在记忆反应期间，抗体γδT细胞和循环T细胞都不足以消除Kp所需的快速宿主防御。相反，通过抛物线共生和耗尽研究证明，exT H17 T RM细胞在细菌清除中发挥重要作用。因此，该研究描述了呼吸道CD4 T RM细胞在细菌感染过程中的起源和功能，为靶向疫苗设计提供了新的策略。
据悉，适应性免疫通过产生中枢和效应性记忆T细胞以及最近描述的组织驻留记忆T (T RM)细胞，提供终生保护。然而，CD4 T RM细胞的细胞起源及其对宿主防御的贡献仍然是未知的。该文章定义了新的组织驻留记忆性细胞的亚群，也就是由TH17细胞发展而来的exTH17细胞。这类细胞经由LEC所分泌的IL-7所滋养调节，并在入侵中起到重要作用。
附：英文原文
Title: Effector TH17 Cells Give Rise to Long-Lived T RM Cells that Are Essential for an Immediate Response against Bacterial Infection
Author: Maria Carolina Amezcua Vesely,Paris Pallis,Piotr Bielecki,Jun Siong Low,Jun Zhao,Christian C.D. Harman,Lina Kroehling,Ruaidhrí Jackson,Will Bailis,Paula Licona-Limón,Hao Xu,Norifumi Iijima,Padmini S. Pillai,Daniel H. Kaplan,Casey T. Weaver,Yuval Kluger,Monika S. Kowalczyk,Akiko Iwasaki,Joao P. Pereira,Enric Esplugues,Nicola Gagliani,Richard A. Flavell
Issue&Volume: Volume 178 Issue 5
Abstract: Adaptive immunity provides life-long protection by generating central and effector memory T cells and the most recently described tissue resident memory T (T RM) cells. However, the cellular origin of CD4 T RM cells and their contribution to host defense remain elusive. Using IL-17A tracking-fate mouse models, we found that a significant fraction of lung CD4 T RM cells derive from IL-17A-producing effector (T H17) cells following immunization with heat-killed Klebsiella pneumonia (Kp). These exT H17 T RM cells are maintained in the lung by IL-7, produced by lymphatic endothelial cells. During a memory response, neither antibodies, γδ T cells, nor circulatory T cells are sufficient for the rapid host defense required to eliminate Kp. Conversely, using parabiosis and depletion studies, we demonstrated that exT H17 T RM cells play an important role in bacterial clearance. Thus, we delineate the origin and function of airway CD4 T RM cells during bacterial infection, offering novel strategies for targeted vaccine design.
DOI: https://doi.org/10.1016/j.cell.2019.07.032
Source: https://www.cell.com/cell/fulltext/S0092-8674(19)30831-1