Human MAIT cells respond to and suppress HIV-1.
Human MAIT cells respond to and suppress HIV-1.
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DOI：
10.7554/elife.50324
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发表时间：
2021-12-24
期刊：
影响因子：
7.7
通讯作者：
Klenerman P
中科院分区：
文献类型：
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作者：
Phetsouphanh C;Phalora P;Hackstein CP;Thornhill J;Munier CML;Meyerowitz J;Murray L;VanVuuren C;Goedhals D;Drexhage L;Moore R;Sattentau QJ;Mak JY;Fairlie DP;Fidler S;Kelleher AD;Frater J;Klenerman P
人类黏膜相关恒定T细胞（MAIT细胞）处于固有免疫和适应性免疫的交界处，具有多功能性，能够通过识别ⅠB类分子MR1来杀伤被病原体感染的细胞。近期研究表明，MAIT细胞在体内具有抗病毒保护作用，因此我们试图探究其在HIV - 1感染中的相关作用。HIV - 1感染者体内的MAIT细胞有显著的活化，在抗逆转录病毒治疗（ART）后活化程度降低。用R5嗜性的HIVBAL刺激THP1单核细胞可在体外强烈激活MAIT细胞。这种激活依赖于白细胞介素 - 12（IL - 12）和白细胞介素 - 18（IL - 18），但不依赖于T细胞受体（TCR）。激活后，MAIT细胞能够上调颗粒酶B、干扰素γ（IFNγ）以及HIV - 1限制因子CCL3、CCL4和CCL5。MAIT细胞产生的限制因子在体外抑制了HIV - 1对原代外周血单个核细胞（PBMCs）和永生化靶细胞的感染。这些数据表明，MAIT细胞是对HIV - 1作出反应的另一类T细胞群体，在控制黏膜部位的病毒复制方面可能具有重要作用。
Human MAIT cells sit at the interface between innate and adaptive immunity, are polyfunctional and are capable of killing pathogen infected cells via recognition of the Class IB molecule MR1. MAIT cells have recently been shown to possess an antiviral protective role in vivo and we therefore sought to explore this in relation to HIV-1 infection. There was marked activation of MAIT cells in vivo in HIV-1-infected individuals, which decreased following ART. Stimulation of THP1 monocytes with R5 tropic HIVBAL potently activated MAIT cells in vitro. This activation was dependent on IL-12 and IL-18 but was independent of the TCR. Upon activation, MAIT cells were able to upregulate granzyme B, IFNγ and HIV-1 restriction factors CCL3, 4, and 5. Restriction factors produced by MAIT cells inhibited HIV-1 infection of primary PBMCs and immortalized target cells in vitro. These data reveal MAIT cells to be an additional T cell population responding to HIV-1, with a potentially important role in controlling viral replication at mucosal sites.