The Role of KLRG1 in Human CIA+ T-Cell Immunity Against Tuberculosis
The Role of KLRG1 in Human CIA+ T-Cell Immunity Against Tuberculosis
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KLRG1 在人类 CD4 T 细胞抗结核免疫中的作用。
DOI：
10.1093/infdis/jiy046
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发表时间：
2018-05-01
影响因子：
6.4
通讯作者：
Fan, Xiao-Yong
中科院分区：
文献类型：
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作者：
Hu, Zhidong;Zhao, Hui-Min;Fan, Xiao-Yong
背景KLRG 1是病毒感染中终末分化的CD 8 + T细胞的标志物，但其在人类结核分枝杆菌感染中的作用仍不清楚。设计了一组结核病患者队列，并在有和无抗体阻断的情况下测定了KLRG 1 CD 4（+）T细胞的表达谱和功能。与健康对照组和非结核病患者相比，活动性结核病患者CD 4（+）T细胞上的KLRG 1表达显著增加。在M。在结核病特异性刺激下，表达KLRG 1的CD 4（+）T细胞分泌干扰素γ、白细胞介素2和肿瘤坏死因子α的能力显著高于表达KLRG的CD 4（+）T细胞，并伴有调节性T细胞比例下降和Akt信号传导增加。然而，表达KLRG 1的CD 4（+）T细胞寿命较短，这与较高的凋亡率有关，但增殖反应相似。阻断KLRG 1信号传导显著增强干扰素γ和白细胞介素2的分泌，而不影响细胞凋亡或增殖。加入一种特异性Akt抑制剂可以阻止这种增加的细胞因子反应，这与Akt信号通路有关。我们的研究描述了结核病患者KLRG 1 CD 4（+）T细胞的分布，并提示M。结核感染促使CD 4（+）T细胞在终末分化状态下获得增强的效应子功能，这通过KLRG 1/Akt信号通路被KLRG 1抑制。
Background. KLRG1 is a marker of terminally differentiated CD8+ T cells in viral infection, but its role in human Mycobacterium tuberculosis infection remains elusive.Methods. A set of cohorts of patients with tuberculosis was designed, and the expression profiles and functions of KLRG1 CD4(+) T cells were determined with and without antibody blocking.RResults. KLRG1 expression on CD4(+) T cells was significantly increased in patients with active tuberculosis, compared with healthy controls and patients without tuberculosis. Upon M. tuberculosis-specific stimulation, the ability to secrete interferon y, interleukin 2, and tumor necrosis factor a was significantly greater in KLRG1-expressing CD4(+) T cells than in their KLRG-negative counterparts and was accompanied by a decreased proportion of regulatory T cells and increased Akt signaling. However, KLRG1expressing CD4(+) T cells had a shorter life-span, which was associated with a higher apoptosis rate but a similar proliferative response. Blockade of KLRG1 signaling significantly enhanced interferon y and interleukin 2 secretion without affecting either cell apoptosis or multiplication. Addition of a specific Akt inhibitor prevented this increased cytokine response, implicating the Akt signaling pathway.Conclusions. Our study delineated the profile of KLRG1 CD4(+) T cells in patients with tuberculosis and suggests that M. tuberculosis infection drives CD4(+) T cells to acquire increased effector function in a terminally differentiated state, which is restrained by KLRG1 via KLRG1/Akt signaling pathway.