在慢性乙型肝炎病毒感染中，PD-1的高表达与循环CD161 ++ TCRiV

StephenW

Front Immunol. 2018 Mar 19;9:472. doi: 10.3389/fimmu.2018.00472. eCollection 2018.
Hyper-Expression of PD-1 Is Associated with the Levels of Exhausted and Dysfunctional Phenotypes of Circulating CD161++TCR iVα7.2+ Mucosal-Associated Invariant T Cells in Chronic Hepatitis B Virus Infection.
Yong YK1,2,3, Saeidi A2, Tan HY1,2,3,4, Rosmawati M2, Enström PF5, Batran RA6, Vasuki V7, Chattopadhyay I8, Murugesan A9, Vignesh R10, Kamarulzaman A2,11, Rajarajeswaran J12, Ansari AW2, Vadivelu J6, Ussher JE13, Velu V14, Larsson M5, Shankar EM11,15,16.
Author information

1
    Laboratory Center, Xiamen University Malaysia, Sepang, Malaysia.
2
    Department of Medicine, University of Malaya Medical Centre, Kuala Lumpur, Malaysia.
3
    China-ASEAN Institute of Marine Science (CAMS), Xiamen University Malaysia, Sepang, Malaysia.
4
    Department of Traditional Chinese Medicine, Xiamen University Malaysia, Sepang, Malaysia.
5
    Division of Molecular Virology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
6
    Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
7
    Department of Microbiology, The Government Thiruvarur Medical College and Hospital, Thiruvarur, India.
8
    Division of Molecular Cancer Biology, Department of Life Sciences, Central University of Tamil Nadu, Thiruvarur, India.
9
    The Government Theni Medical College and Hospital, Theni, India.
10
    Laboratory-Based Department, Universiti Kuala Lumpur, Ipoh, Malaysia.
11
    Center of Excellence for Research in AIDS, University of Malaya, Kuala Lumpur, Malaysia.
12
    Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
13
    Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.
14
    Department of Microbiology and Immunology, Emory Vaccine Center, Atlanta, GA, United States.
15
    Division of Infection Biology, Department of Life Sciences, Central University of Tamil Nadu, Thiruvarur, India.
16
    Department of Microbiology, Central University of Tamil Nadu, Thiruvarur, India.

Abstract

Mucosal-associated invariant T (MAIT) cells, defined as CD161++TCR iVα7.2+ T cells, play an important role in the innate defense against bacterial infections, and their functionality is impaired in chronic viral infections. Here, we investigated the frequency and functional role of MAIT cells in chronic hepatitis B virus (HBV) infection. The peripheral CD3+CD161++TCR iVα7.2+ MAIT cells in chronic HBV-infected patients and healthy controls were phenotypically characterized based on CD57, PD-1, TIM-3, and CTLA-4, as well as HLA-DR and CD38 expression. The frequency of MAIT cells was significantly decreased among chronic HBV-infected individuals as compared to controls. Expression of CD57, PD-1, CTLA-4, as well as HLA-DR and CD38 on MAIT cells was significantly elevated in chronic HBV-infected individuals relative to controls. The percentage of T cell receptor (TCR) iVα7.2+ CD161+ MAIT cells did not correlate with HBV viral load but inversely with HLA-DR on CD4+ T cells and MAIT cells and with CD57 on CD8+ T cells suggesting that decrease of MAIT cells may not be attributed to direct infection by HBV but driven by HBV-induced chronic immune activation. The percentage and expression levels of PD-1 as well as CTLA-4 on MAIT cells inversely correlated with plasma HBV-DNA levels, which may suggest either a role for MAIT cells in the control of HBV infection or the effect of HBV replication in the liver on MAIT cell phenotype. We report that decrease of TCR iVα7.2+ MAIT cells in the peripheral blood and their functions were seemingly impaired in chronic HBV-infected patients likely because of the increased expression of PD-1.
KEYWORDS:

CTLA-4; HBV infection; HLA-DR; PD-1; immune exhaustion; immunosenescence; mucosal-associated invariant T cells

PMID:
    29616020
PMCID:
    PMC5868455
DOI:
    10.3389/fimmu.2018.00472

StephenW

Front Immunol。 2018年3月19日; 9：472。 doi：10.3389 / fimmu.2018.00472。 eCollection 2018年。
在慢性乙型肝炎病毒感染中，PD-1的高表达与循环CD161 ++ TCRiVα7.2+粘膜相关不变T细胞的耗尽和功能失调表型的水平相关联。
Yong YK1,2,3 Saeidi A2 Tan Tan1,2,3,4 Rosmawati M2EnströmPF5 Batran RA6 Vasuki V7 Chattopadhyay I8 Murugesan A9 Vignesh R10 Kamarulzaman A2,11 Rajarajeswaran J12 Ansari AW2 ，Vadivelu J6，Ussher JE13，Velu V14，Larsson M5，Shankar EM11,15,16。
作者信息

1
    厦门大学实验中心，马来西亚雪邦。
2
    马来亚大学医学中心医学系，吉隆坡，马来西亚。
3
    中国 - 东盟海洋科学研究所（CAMS），马来西亚厦门大学，马来西亚雪邦。
4
    厦门大学中医系，马来西亚雪邦。
五
    瑞典林雪平林雪平大学临床与实验医学系分子病毒学系。
6
    马来西亚吉隆坡马来亚大学医学院医学微生物学系。
7
    印度Thiruvarur Thiruvarur医学院和医院微生物学系。
8
    分子癌症生物学部，印度蒂鲁瓦尔的泰米尔纳德邦中央大学生命科学系。
9
    政府Theni医学院和医院，印度Theni。
10
    马来西亚怡保吉隆坡大学实验室部门。
11
    马来西亚吉隆坡大学艾滋病研究卓越中心。
12
    马来西亚吉隆坡大学医学院分子医学系。
13
    新西兰达尼丁奥塔哥大学微生物与免疫学系。
14
    美国佐治亚州亚特兰大Emory疫苗中心微生物和免疫学系。
15
    感染生物学部，印度蒂鲁瓦尔的泰米尔纳德邦中央大学生命科学系。
16
    印度Thiruvarur泰米尔纳德邦中央大学微生物系。

抽象

定义为CD161 ++ TCRiVα7.2+ T细胞的粘膜相关不变T细胞（MAIT）在天然防御细菌感染中起重要作用，并且其功能在慢性病毒感染中受损。在这里，我们调查了MAIT细胞在慢性乙型肝炎病毒（HBV）感染中的频率和功能作用。在慢性HBV感染患者和健康对照中的外周CD3 + CD161 ++ TCRiVα7.2+ MAIT细胞基于CD57，PD-1，TIM-3和CTLA-4以及HLA-DR和CD38表达。与对照组相比，慢性HBV感染者中MAIT细胞的频率显着降低。 CD57，PD-1，CTLA-4以及HLA-DR和CD38在MAIT细胞上的表达在慢性HBV感染的个体中相对于对照显着升高。 T细胞受体（TCR）iVα7.2+ CD161 + MAIT细胞的百分比与HBV病毒载量无关，但与CD4 + T细胞和MAIT细胞上的HLA-DR以及CD8 + T细胞上的CD57呈负相关，表明MAIT细胞的减少可能不归因于HBV直接感染，而是由HBV诱导的慢性免疫激活所驱动。在MAIT细胞中PD-1和CTLA-4的百分比和表达水平与血浆HBV-DNA水平呈负相关，这可能表明MAIT细胞在控制HBV感染中的作用或者在HBV感染肝对MAIT细胞表型的影响。我们报告，外周血中TCRiVα7.2+ MAIT细胞的减少及其功能在慢性HBV感染患者中似乎受损，这可能是由于PD-1表达增加。
关键词：

CTLA-4; HBV感染; HLA-DR; PD-1;免疫力衰竭;免疫衰老;粘膜相关不变T细胞

结论：
    29616020
PMCID：
    PMC5868455
DOI：
    10.3389 / fimmu.2018.00472