Immune Checkpoint Molecules Expressed on CD4+ T Cell Subsets in Chronic Asymptomatic Hepatitis B Virus Carriers With Hepatitis B e Antigen-Negative

Dawei Cui; Daixi Jiang; Cuilin Yan; Xia Liu; Yan Lv; Jue Xie; Yu Chen

doi:10.3389/fmicb.2022.887408

Immune Checkpoint Molecules Expressed on CD4⁺ T Cell Subsets in Chronic Asymptomatic Hepatitis B Virus Carriers With Hepatitis B e Antigen-Negative

Front Microbiol. 2022 Apr 27:13:887408. doi: 10.3389/fmicb.2022.887408. eCollection 2022.

Authors

Dawei Cui^{1

2}, Daixi Jiang³, Cuilin Yan¹, Xia Liu⁴, Yan Lv², Jue Xie², Yu Chen¹

Affiliations

¹ Department of Laboratory Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Institute of Laboratory Medicine, Zhejiang University, Hangzhou, China.
² Department of Blood Transfusion, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
³ State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
⁴ ZJU-Hangzhou Global Scientific and Technological Innovation Center, Hangzhou, China.

Abstract

Background: Chronic hepatitis B virus (HBV) infection remains a major public health problem worldwide. Immune checkpoint molecules expressed on CD4⁺ T cells play critical roles in chronic HBV infection. However, their roles in chronic asymptomatic HBV carriers (ASCs) with hepatitis B e antigen (HBeAg)-negative remain unclear. In this study, we explored the role of immune checkpoint molecules expressed on CD4⁺ T cell subsets in chronic ASCs with HBeAg-negative.

Methods: Human peripheral blood mononuclear cells (PBMCs) from the ASCs with HBeAg-negative and healthy controls (HC) were isolated, and immune checkpoint molecules expressed on CD4⁺ T cell subsets and serum cytokines were detected by flow cytometry. Moreover, the mRNA expressions of immune checkpoint molecules were analyzed by a real-time quantitative PCR assay.

Results: In comparison with HC, CD4⁺ T cells highly expressed LAG-3, TIM-3, and PD-1 in PBMCs from chronic ASCs with HBeAg-negative. Interestingly, the expressions of TIM-3 and PD-1 on circulating follicular helper T (Tfh) cells in ASCs were significantly high. Moreover, high expressions of LAG-3, TIM-3, and PD-1 were different among Treg, Th1, Th2, and Th17 cells. In addition, the expressions of TIM-3 and CTLA-4 mRNA in PBMCs from ASCs were significantly elevated. However, the frequency of CTLA-4⁺CD4⁺ T cell subsets in PBMCs from ASCs was not different from HC. The levels of six cytokines in serum from ASCs were not clearly different from HC.

Conclusion: Immune checkpoint molecules highly expressed on CD4⁺ T cell subsets indicated an important role in chronic ASCs with HBeAg-negative, which provided potential therapeutic targets in the pathogenesis of chronic HBV infection.

Keywords: CD4+ T cells; asymptomatic HBV carriers; chronic hepatitis B virus; hepatitis B virus; immune checkpoint molecules.