Cutting Edge: Characterization of Human Tissue-Resident Memory T Cells at Different Infection Sites in Patients with Tuberculosis
Cutting Edge: Characterization of Human Tissue-Resident Memory T Cells at Different Infection Sites in Patients with Tuberculosis
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前沿技术：结核病患者不同感染部位的人体组织驻留记忆 T 细胞的表征
DOI：
10.4049/jimmunol.1901326
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发表时间：
2020-05-01
影响因子：
4.4
通讯作者：
Ma, Li
中科院分区：
文献类型：
--
作者：
Yang, Qianting;Zhang, Mingxia;Ma, Li
结核病患者在不同感染部位表现出高频率的trm。这些TRMs表现出记忆，具有激活和多功能表型。TRMs限制巨噬细胞内结核分枝杆菌的复制。组织驻留记忆T细胞（TRMs）在介导小鼠对结核病（TB）的宿主防御中起着关键作用，但它们在人类中的对应体尚未得到很好的表征。在本文中，我们招募了结核病患者，并通过流式细胞术或大规模细胞术测定了不同感染部位（包括外周血、胸膜液、支气管肺泡灌洗液和肺）的TRM频率、转运、激活标记物表达和细胞因子产生。我们发现除了外周血外，所有感染部位TRMs的频率都很高。这些TRMs表现出记忆表型，高度激活（基于CD38和HLA-DR表达），表达高水平的运输（CCR5和CXCR6）和衰竭（PD-1）标记。当受结核分枝杆菌刺激时，TRMs分泌包括IFN-γ、TNF-α和IL-2在内的细胞因子，并表现出多功能表型。TRMs限制巨噬细胞内结核分枝杆菌的复制。这些数据告诉我们目前对结核病患者不同感染部位免疫监测的了解。
Key Points Patients with TB exhibit a high frequency of TRMs at different infection sites. These TRMs exhibit memory, with an activated and multifunctional phenotype. TRMs limit intracellular M. tuberculosis replication in macrophages. Tissue-resident memory T cells (TRMs) have a key role in mediating the host defense against tuberculosis (TB) in mice, but their human counterparts have not been well characterized. In this article, we recruited patients with TB and determined TRM frequency, trafficking, activation marker expression, and cytokine production by flow or mass cytometry at different infection sites, including peripheral blood, pleural fluid, bronchoalveolar lavage fluid, and lung. We found a high frequency of TRMs at all infection sites apart from the peripheral blood. These TRMs exhibited a memory phenotype, were highly activated (based on CD38 and HLA-DR expression), and expressed high levels of trafficking (CCR5 and CXCR6) and exhaustion (PD-1) markers. When stimulated with Mycobacterium tuberculosis, TRMs secreted cytokines, including IFN-γ, TNF-α, and IL-2, and exhibited a multifunctional phenotype. TRMs limited intracellular M. tuberculosis replication in macrophages. These data inform our current understanding of immunosurveillance at different infection sites in patients with TB.