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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.

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
[Indexed for MEDLINE]
Free PMC Article

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