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.
Highlights
Hepatitis B virus (HBV) infection remains a major threat worldwide with ~240 million people chronically infected, and estimates suggest that ~780,000 die annually due to complications including cirrhosis, hepatocellular carcinoma (HCC), and chronic liver failure [1]
The three groups, non-randomized study design consisted of samples from 21 subjects with chronic hepatitis B virus (HBV) infection: Group 1 (G1) CHB DNAemia positive, G2 with 9 CHB DNAemia negative, and a control group (G3) of healthy controls (HCs)
Given that the T cell receptor (TCR) Vα7.2+ Mucosal-associated invariant T (MAIT) cells are found in circulation and enriched in mucosal compartment and liver, we postulate that the levels of immune exhaustion on MAIT cells are secondary to ongoing HBV infection and may hamper HBV viral clearance
Summary
Hepatitis B virus (HBV) infection remains a major threat worldwide with ~240 million people chronically infected, and estimates suggest that ~780,000 die annually due to complications including cirrhosis, hepatocellular carcinoma (HCC), and chronic liver failure [1]. Despite the availability of an effective prophylactic vaccine, a smaller fraction of vaccinated individuals (~2%) in endemic regions can still be chronically infected with HBV [2]. Prophylactic vaccines have little or no effect on those who have already been chronically infected with HBV [3, 4]. The therapeutic goal in chronic HBV infection is to achieve sustained suppression of viral replication and thereby reduce liver disease progression and the risk of clinical end-points. Despite potent antiviral drugs that inhibit HBV reverse transcriptase, “complete” virological response, defined as hepatitis B surface antigen (HBsAg) clearance, is rarely achieved [5,6,7]. Virus eradication is seldom achieved and patients experience viral rebound after withdrawal of antiviral therapy [2]
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