Peripheral loss of CD8+CD161++TCRV7•2+ mucosal-associated invariant T cells in chronic hepatitis C virus-infected patients

被引：68

作者：

Barathan, Muttiah ^{[1
]}

Mohamed, Rosmawati ^{[2
]}

Vadivelu, Jamuna ^{[1
]}

Chang, Li Y. ^{[1
]}

Saeidi, Alireza ^{[1
]}

Yong, Yean K. ^{[2
]}

Ram, M. Ravishankar ^{[1
]}

Gopal, Kaliappan ^{[3
]}

Velu, Vijayakumar ^{[4
]}

Larsson, Marie ^{[5
]}

Shankar, Esaki M. ^{[1
,6
]}

机构：

[1] Univ Malaya, Dept Med Microbiol, TIDREC, Fac Med, Kuala Lumpur 50603, Malaysia

[2] Univ Malaya, Dept Med, Kuala Lumpur 50603, Malaysia

[3] Univ Malaya, Dept Orthopaed Surg, TEG, NOCERAL,Fac Med, Kuala Lumpur 50603, Malaysia

[4] Emory Vaccine Ctr, Dept Microbiol & Immunol, 954 Gatewood Rd, Atlanta, GA 30329 USA

[5] Linkoping Univ, Dept Clin & Expt Med, Div Mol Virol, S-58185 Linkoping, Sweden

[6] Univ Malaya, CERiA, Kuala Lumpur 50603, Malaysia

来源：

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION | 2016年 / 46卷 / 02期

基金：

瑞典研究理事会;

关键词：

CD38; exhaustion; HCV infection; MAIT cells; PD-1; TCRV alpha 7.2; CD161; EXPRESSION; PD-1; PATHWAYS; DEFINES; SUBSET; CCR5;

D O I：

10.1111/eci.12581

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

BackgroundMucosal-associated invariant T (MAIT) cells play an important role in innate host defence. MAIT cells appear to undergo exhaustion and are functionally weakened in chronic viral infections. However, their role in chronic hepatitis C virus (HCV) infection remains unclear. Materials and methodsWe investigated the frequency of CD8(+)CD161(++)TCR V7.2(+) MAIT cells in a cross-sectional cohort of chronic HCV-infected patients (n = 25) and healthy controls (n = 25). Peripheral blood mononuclear cells were investigated for circulating MAIT cell frequency, liver-homing (CCR5 and CD103), biomarkers of immune exhaustion (PD-1, TIM-3 and CTLA-4), chronic immune activation (CD38 and HLA-DR), and immunosenescence (CD57) by flow cytometry. ResultsThe frequency of MAIT cells was significantly decreased, and increased signs of immune exhaustion and chronic immune activation were clearly evident on MAIT cells of HCV-infected patients. Decrease of CCR5 on circulating MAIT cells is suggestive of their peripheral loss in chronic HCV-infected patients. MAIT cells also showed significantly increased levels of HLA-DR, CD38, PD-1, TIM-3 and CTLA-4, besides CD57 in chronic HCV disease. ConclusionsImmune exhaustion and senescence of CD8(+)CD161(++)TCR V7.2(+) MAIT cells could contribute to diminished innate defence attributes likely facilitating viral persistence and HCV disease progression.

引用

页码：170 / 180

页数：11

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