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Analysis of HBV-Specific CD4 T-cell Responses and Identification of HLA-DR-Restricted CD4 T-Cell Epitopes Based on a Peptide Matrix
Published on: October 20, 2021
Immune Checkpoint Molecules Expressed on CD4+ T Cell Subsets in Chronic Asymptomatic Hepatitis B Virus Carriers With
Dawei Cui1,2, Daixi Jiang3, Cuilin Yan1
1Department 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.
Insights
Immune checkpoint molecules like LAG-3, TIM-3, and PD-1 are highly expressed on CD4+ T cells in chronic asymptomatic hepatitis B carriers (ASCs). This finding suggests potential therapeutic targets for chronic HBV infection.
Area of Science:
- Immunology
- Hepatology
- Virology
Background:
- Chronic hepatitis B virus (HBV) infection is a global health concern.
- Immune checkpoint molecules on CD4+ T cells are crucial in chronic HBV.
- Their role in HBeAg-negative asymptomatic carriers (ASCs) is not well understood.
Purpose of the Study:
- To investigate immune checkpoint molecule expression on CD4+ T cell subsets in HBeAg-negative chronic HBV ASCs.
- To identify potential therapeutic targets for chronic HBV infection.
Main Methods:
- Peripheral blood mononuclear cells (PBMCs) from ASCs and healthy controls (HC) were analyzed.
- Flow cytometry was used to detect immune checkpoint molecules on CD4+ T cell subsets.
- Real-time quantitative PCR analyzed mRNA expression of immune checkpoint molecules.
Main Results:
- CD4+ T cells in ASCs showed higher expression of LAG-3, TIM-3, and PD-1 compared to HC.
- Follicular helper T (Tfh) cells in ASCs exhibited significantly high TIM-3 and PD-1 expression.
- TIM-3 and CTLA-4 mRNA levels were elevated in ASCs, though CTLA-4+ CD4+ T cell frequency did not differ.
Conclusions:
- High expression of immune checkpoint molecules on CD4+ T cell subsets is significant in HBeAg-negative chronic HBV ASCs.
- These molecules represent potential therapeutic targets for managing chronic HBV infection.
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.
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