AUTHOR=Cui Dawei , Jiang Daixi , Yan Cuilin , Liu Xia , Lv Yan , Xie Jue , Chen Yu 

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

JOURNAL=Frontiers in Microbiology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.887408

DOI=10.3389/fmicb.2022.887408

ISSN=1664-302X

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. Here, we explore the role of immune checkpoint molecules expressed on CD4+T cell subsets in chronic ASCs with HBeAg-negative. 
Method: Human peripheral blood mononuclear cells (PBMCs) from the chronic asymptomatic HBV carriers 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 real-time quantitative PCR assay. 
Result: 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, respectively. Moreover, high expressions of LAG-3, TIM-3, and PD-1 were obviously different among Treg, Th1, Th2, and Th17 cells, respectively. Additionally, 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 obviously 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.