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

BMC Immunology
Yuejiao DongYu Chen

Abstract

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. 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. 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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Citations

Oct 23, 2019·Frontiers in Immunology·Weiting QinXu Wang
Apr 9, 2020·Frontiers in Immunology·Jil M JubelFrank A Schildberg
Jul 30, 2020·Viruses·Sylwia OsuchKamila Caraballo Cortés
Sep 16, 2020·Journal for Immunotherapy of Cancer·Takumi MaruhashiTaku Okazaki
Sep 25, 2020·Viruses·Huiming CaiQinchang Zhu
Dec 19, 2020·Frontiers in Microbiology·Tanveer AhmadSyed Mansoor Ali
Aug 18, 2020·International Journal of Radiation Oncology, Biology, Physics·Roshal R PatelJames W Welsh
Mar 30, 2021·Frontiers in Immunology·Rafael de Freitas E Silva, Esther von Stebut
Nov 2, 2020·Experimental Gerontology·Mirjana Nacka-AleksićGordana Leposavić
Jun 3, 2021·International Journal of Molecular Sciences·Arshi KhanamShyam Kottilil
Jun 3, 2021·Cells·Sonja I Buschow, Diahann T S L Jansen
Jun 30, 2021·Journal of Clinical Pathology·Mark P LythgoeAdam Enver Frampton
Jun 18, 2021·World Journal of Gastroenterology : WJG·Efthymios P TsounisChristos Triantos
Jul 9, 2021·Experimental Biology and Medicine·Stefan SemanDejana Popović
Oct 14, 2021·International Journal of Molecular Sciences·Shubhangi GavaliMagdalena Paolino

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Methods Mentioned

BETA
flow cytometry
ELISA
PCR
density gradient centrifugation

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