Regulatory B Cells Dysregulated T Cell Function in an IL-35-Dependent Way in Patients With Chronic Hepatitis B
Open Access
- 12 April 2021
- journal article
- research article
- Published by Frontiers Media SA in Frontiers in Immunology
Abstract
Interleukin (IL)-35-secreting B (IL-35+B) cells are critical regulators in autoimmune and infectious diseases and exert suppressive functions in parallel with IL-10-producing B (B10) cells. However, the role of IL-35+B cells in persistent hepatitis B virus (HBV) infection remains unclear. To elucidate the role of IL-35+B cells in the progress of chronic HBV infection, we determined the frequency of IL-35+B cells and their relationship with the classical human regulatory B cell (Breg) subsets, namely, CD19+CD24hiCD38hi and CD19+CD24hiCD27+. Then, the regulatory effect and mechanism of Bregs on effector T cells were investigated in vitro. Here, we found that compared with healthy controls, the frequency of IL-35+B cells was increased in patients with chronic HBV infection and was enriched in human classical Breg subset CD19+CD24hiCD38hi B cells. Moderate correlation was observed between the frequency of IL-35+B cells and alanine aminotransferase levels (Spearman r = 0.401), but only mild correlation was noted between the frequency of IL-35+B cells and HBV DNA level (Spearman r = 0.314). The frequency of IL-35+B cells was negatively correlated with interferon-γ (IFN-γ)-producing CD4+ and CD8+ cells but positively correlated with IL-4-producing T cells. Bregs dysregulated T cell function through an IL-35-dependent mechanism and depended on cell-to-cell contact. In conclusion, IL-35+ B cell was enriched in CD19+CD24hiCD38hi B cell subset during persistent HBV infection and Breg cells exerted dysregulation in T cell function through IL-35 dependent mechanism and depend on cell-to-cell contact. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT03734783.Funding Information
- Natural Science Foundation of Shanghai
- Natural Science Foundation of Shanghai
- Wu Jieping Medical Foundation
This publication has 31 references indexed in Scilit:
- IL-10–Producing Regulatory B Cells in the Pathogenesis of Chronic Hepatitis B Virus InfectionThe Journal of Immunology, 2012
- Regulatory B cells control T-cell autoimmunity through IL-21-dependent cognate interactionsNature, 2012
- Tumor-Evoked Regulatory B Cells Promote Breast Cancer Metastasis by Converting Resting CD4+ T Cells to T-Regulatory CellsCancer Research, 2011
- IL‐10 produced by activated human B cells regulates CD4+ T‐cell activation in vitroEuropean Journal of Immunology, 2010
- Nonredundant Roles for B Cell-Derived IL-10 in Immune Counter-RegulationThe Journal of Immunology, 2009
- Characterization of Hepatitis B Virus (HBV)-Specific T-Cell Dysfunction in Chronic HBV InfectionJournal of Virology, 2007
- B7-H1 expression is upregulated in peripheral blood CD14+ monocytes of patients with chronic hepatitis B virus infection, which correlates with higher serum IL-10 levelsJournal of Viral Hepatitis, 2006
- Restoring function in exhausted CD8 T cells during chronic viral infectionNature, 2005
- Regulatory T cells contribute to the impaired immune response in patients with chronic hepatitis B virus infectionJournal of Hepatology, 2005
- B cells regulate autoimmunity by provision of IL-10Nature Immunology, 2002