Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), Faculty of Health Sciences, Institute of Infectious Disease and Molecular Medicine (IDM), University of Cape Town, Cape Town, South Africa.
Front Immunol. 2021 Mar 22;12:648216. doi: 10.3389/fimmu.2021.648216. eCollection 2021.
MAIT cells are non-classically restricted T lymphocytes that recognize and rapidly respond to microbial metabolites or cytokines and have the capacity to kill bacteria-infected cells. Circulating MAIT cell numbers generally decrease in patients with active TB and HIV infection, but findings regarding functional changes differ. We conducted a cross-sectional study on the effect of HIV, TB, and HIV-associated TB (HIV-TB) on MAIT cell frequencies, activation and functional profile in a high TB endemic setting in South Africa. Blood was collected from (i) healthy controls (HC, = 26), 24 of whom had LTBI, (ii) individuals with active TB (aTB, = 36), (iii) individuals with HIV infection (HIV, = 50), 37 of whom had LTBI, and (iv) individuals with HIV-associated TB (HIV-TB, = 26). All TB participants were newly diagnosed and sampled before treatment, additional samples were also collected from 18 participants in the aTB group after 10 weeks of TB treatment. Peripheral blood mononuclear cells (PBMC) stimulated with BCG-expressing GFP (BCG-GFP) and heat-killed (HK) () were analyzed using flow cytometry. MAIT cells were defined as CD3 CD161 Vα7.2 T cells. Circulating MAIT cell frequencies were depleted in individuals with HIV infection ( = 0.009). MAIT cells showed reduced CD107a expression in aTB ( = 0.006), and reduced IFNγ expression in aTB ( < 0.001) and in HIV-TB ( < 0.001) in response to BCG-GFP stimulation. This functional impairment was coupled with a significant increase in activation (defined by HLA-DR expression) in resting MAIT cells from HIV ( < 0.001), aTB ( = 0.019), and HIV-TB ( = 0.005) patients, and higher HLA-DR expression in MAIT cells expressing IFNγ in aTB ( = 0.009) and HIV-TB ( = 0.002) after stimulation with BCG-GFP and HK-. After 10 weeks of TB treatment, there was reversion in the observed functional impairment in total MAIT cells, with increases in CD107a ( = 0.020) and IFNγ ( = 0.010) expression. Frequencies and functional profile of MAIT cells in response to mycobacterial stimulation are significantly decreased in HIV infected persons, active TB and HIV-associated TB, with a concomitant increase in MAIT cell activation. These alterations may reduce the capacity of MAIT cells to play a protective role in the immune response to these two pathogens.
MAIT 细胞是一种非经典受限的 T 淋巴细胞，能够识别和快速响应微生物代谢物或细胞因子，并具有杀死被细菌感染的细胞的能力。在活动性结核和 HIV 感染患者中，循环 MAIT 细胞数量通常会减少，但功能变化的研究结果存在差异。我们在南非一个高结核流行地区进行了一项横断面研究，以研究 HIV、TB 和 HIV 相关 TB（HIV-TB）对 MAIT 细胞频率、激活和功能特征的影响。血液取自：（i）健康对照者（HC，n=26），其中 24 人为 LTBI；（ii）活动性结核患者（aTB，n=36）；（iii）HIV 感染者（HIV，n=50），其中 37 人为 LTBI；（iv）HIV 相关 TB 患者（HIV-TB，n=26）。所有 TB 患者均为新诊断且在治疗前采样，aTB 组的 18 名患者在接受 10 周 TB 治疗后也采集了额外的样本。使用流式细胞术分析经 BCG 表达 GFP（BCG-GFP）和热灭活（HK）刺激的外周血单核细胞（PBMC）。MAIT 细胞定义为 CD3 CD161 Vα7.2 T 细胞。HIV 感染者的循环 MAIT 细胞频率降低（=0.009）。在 aTB 患者中，MAIT 细胞的 CD107a 表达降低（=0.006），在 aTB 患者和 HIV-TB 患者中 IFNγ 表达降低（BCG-GFP 刺激时，<0.001）。这种功能障碍与 HIV（<0.001）、aTB（=0.019）和 HIV-TB（=0.005）患者静息 MAIT 细胞的活化（定义为 HLA-DR 表达）显著增加有关，并且在 BCG-GFP 和 HK-刺激后，表达 IFNγ 的 MAIT 细胞中 HLA-DR 表达也更高 aTB（=0.009）和 HIV-TB（=0.002）。在接受 10 周 TB 治疗后，总 MAIT 细胞的观察到的功能障碍得到逆转，CD107a（=0.020）和 IFNγ（=0.010）表达增加。在 HIV 感染、活动性 TB 和 HIV 相关 TB 患者中，MAIT 细胞对分枝杆菌刺激的频率和功能特征显著降低，同时 MAIT 细胞的活化增加。这些改变可能会降低 MAIT 细胞在对这两种病原体的免疫反应中发挥保护作用的能力。
