Functional and Activation Profiles of Mucosal-Associated Invariant T Cells in Patients With Tuberculosis and HIV in a High Endemic Setting.
Functional and Activation Profiles of Mucosal-Associated Invariant T Cells in Patients With Tuberculosis and HIV in a High Endemic Setting.
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DOI：
10.3389/fimmu.2021.648216
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发表时间：
2021
影响因子：
7.3
通讯作者：
Shey M
中科院分区：
文献类型：
--
作者：
Balfour A;Schutz C;Goliath R;Wilkinson KA;Sayed S;Sossen B;Kanyik JP;Ward A;Ndzhukule R;Gela A;Lewinsohn DM;Lewinsohn DA;Meintjes G;Shey M
背景资料：MAIT细胞是非经典限制性T淋巴细胞，其识别并快速响应微生物代谢物或细胞因子，并具有杀死细菌感染细胞的能力。在活动性结核病和HIV感染患者中，循环MAIT细胞数量通常会减少，但关于功能变化的研究结果不同。研究方法：我们在南非结核病高发地区进行了一项关于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的横断面研究。血液采集自（i）健康对照（HC，n = 26），其中24人患有LTBI，（ii）患有活动性TB的个体（aTB，n = 36），（iii）患有HIV感染的个体（HIV，n = 50），其中37人患有LTBI，和（iv）患有HIV相关TB的个体（HIV-TB，n = 26）。所有结核病参与者都是在治疗前新诊断和采样的，在结核病治疗10周后，还从aTB组的18名参与者中收集了额外的样本。用流式细胞术分析用BCG表达GFP（BCG-GFP）和热灭活（HK）结核分枝杆菌（M.tb）刺激的外周血单个核细胞（PBMC）。MAIT细胞定义为CD 3 + CD 161 + Vα7.2+ T细胞。结果：HIV感染者的循环MAIT细胞频率减少（p = 0.009）。MAIT细胞在aTB中显示出降低的CD 107 a表达（p = 0.006），并且在aTB（p < 0.001）和HIV-TB（p < 0.001）中响应于BCG-GFP刺激而显示出降低的IFNγ表达。这种功能障碍伴随着激活的显著增加，（由HLA-DR表达定义）（p < 0.001），aTB（p = 0.019），以及艾滋病毒/结核病（p = 0.005）患者，在用BCG-GFP和HK-M. tb刺激后，在aTB（p = 0.009）和HIV-TB（p = 0.002）中表达IFNγ的MAIT细胞中HLA-DR表达更高。TB治疗10周后，观察到的总MAIT细胞的功能损害逆转，CD 107 a（p = 0.020）和IFNγ（p = 0.010）表达增加。结论：在HIV感染者、活动性TB和HIV相关TB中，MAIT细胞响应于分枝杆菌刺激的频率和功能谱显著降低，伴随着MAIT细胞活化的增加。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。
Background: 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. Methods: 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, n = 26), 24 of whom had LTBI, (ii) individuals with active TB (aTB, n = 36), (iii) individuals with HIV infection (HIV, n = 50), 37 of whom had LTBI, and (iv) individuals with HIV-associated TB (HIV-TB, n = 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) Mycobacterium tuberculosis (M.tb) were analyzed using flow cytometry. MAIT cells were defined as CD3+ CD161+ Vα7.2+ T cells. Results: Circulating MAIT cell frequencies were depleted in individuals with HIV infection (p = 0.009). MAIT cells showed reduced CD107a expression in aTB (p = 0.006), and reduced IFNγ expression in aTB (p < 0.001) and in HIV-TB (p < 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 (p < 0.001), aTB (p = 0.019), and HIV-TB (p = 0.005) patients, and higher HLA-DR expression in MAIT cells expressing IFNγ in aTB (p = 0.009) and HIV-TB (p = 0.002) after stimulation with BCG-GFP and HK-M.tb. After 10 weeks of TB treatment, there was reversion in the observed functional impairment in total MAIT cells, with increases in CD107a (p = 0.020) and IFNγ (p = 0.010) expression. Conclusions: 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.
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影响因子：
4
作者：
Gherardin NA;Souter MN;Koay HF;Mangas KM;Seemann T;Stinear TP;Eckle SB;Berzins SP;d'Udekem Y;Konstantinov IE;Fairlie DP;Ritchie DS;Neeson PJ;Pellicci DG;Uldrich AP;McCluskey J;Godfrey DI
通讯作者：
Godfrey DI
影响因子：
30.5
作者：
Le Bourhis, Lionel;Martin, Emmanuel;Lantz, Olivier
通讯作者：
Lantz, Olivier
DOI：
10.4049/jimmunol.1101122
发表时间：
2011-09-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Day CL;Abrahams DA;Lerumo L;Janse van Rensburg E;Stone L;O'rie T;Pienaar B;de Kock M;Kaplan G;Mahomed H;Dheda K;Hanekom WA
通讯作者：
Hanekom WA
影响因子：
5.4
作者：
Amelio, Patrizia;Portevin, Damien;Perreau, Matthieu
通讯作者：
Perreau, Matthieu
影响因子：
6.7
作者：
Le Bourhis L;Dusseaux M;Bohineust A;Bessoles S;Martin E;Premel V;Coré M;Sleurs D;Serriari NE;Treiner E;Hivroz C;Sansonetti P;Gougeon ML;Soudais C;Lantz O
通讯作者：
Lantz O