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BMC Immunology
Published in: BMC Immunology 1/2019

Open Access 01-12-2019 | Hepatitis B | Research article

CD4+ T cell exhaustion revealed by high PD-1 and LAG-3 expression and the loss of helper T cell function in chronic hepatitis B

Authors: Yuejiao Dong, Xuefen Li, Lu Zhang, Qiaoyun Zhu, Chunlei Chen, Jiaqi Bao, Yu Chen

Published in: BMC Immunology | Issue 1/2019

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Abstract

Background

Immune inhibitory receptors play an important role in chronic infections. However, little is known about their role in hepatitis B virus (HBV) infection. Here, we analyzed the relationship between programmed death-1 (PD-1) and lymphocyte activation gene-3 (LAG-3) expression on CD4+ T cells and HBV disease progression.

Results

PD-1 and LAG-3 expression was significantly higher on CD4+ T cells from HBV patients than on those from the HCs. In addition, a significant positive correlation was found between the PD-1 and LAG-3 expression levels and the ALT(alanine aminotransferase) level. CD4+ T cell function was inhibited by high PD-1 and LAG-3 levels, and CD4+ T cells with high PD-1 and LAG-3 expression lost the ability to secrete IFN-γ, IL-2 and TNF-α. Furthermore, blockade of the PD-1 and LAG-3 pathways reversed the damage to CD4+ T cell proliferation and cytokine secretion.

Conclusions

CD4+ T cell exhaustion during chronic HBV had high PD-1 and LAG-3 expression and the absence of helper T cell cytokines, including IFN-γ, IL-2 and TNF-α. After blocking PD-L1 and LAG-3, CD4+ T cell function in chronic hepatitis B patients was partially restored.
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Metadata
Title
CD4+ T cell exhaustion revealed by high PD-1 and LAG-3 expression and the loss of helper T cell function in chronic hepatitis B
Authors
Yuejiao Dong
Xuefen Li
Lu Zhang
Qiaoyun Zhu
Chunlei Chen
Jiaqi Bao
Yu Chen
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Immunology / Issue 1/2019
Electronic ISSN: 1471-2172
DOI
https://doi.org/10.1186/s12865-019-0309-9

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