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Role of IL-10-Producing Regulatory B Cells in Chronic Hepatitis B Virus Infection

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Abstract

Background

A subset of interleukin (IL)-10-producing regulatory B (Breg) cells that suppress T-cell-mediated immunity was recently identified; however, their role in chronic hepatitis B (CHB) remains elusive.

Aim

To explore the possible role of Breg in the interaction with Th cells and consequent pathogenesis of CHB.

Methods

The prevalence of Breg as well as 3 major effector T-cell subsets—CD4+CD25highFoxp3+ regulatory T (Treg) cells, T helper 1 cells (Th1), and T helper 2 cells (Th2)—was assessed in the peripheral blood of 31 patients with CHB, 28 patients with acute hepatitis B (AHB), and 25 healthy controls (HC).

Results

Compared to patients with AHB and HC, the prevalence of Breg and Treg cells and the concentration of IL-10 in the supernatant of cultured peripheral blood mononuclear cells (PBMCs) were greatly increased in patients with CHB. A significantly decreased proportion of Th1 cells was also observed in patients with CHB and was demonstrated to have a negative correlation with the prevalence of Breg. Furthermore, depletion of Treg cells in the PBMCs of patients with CHB did not alter the frequency of Breg cells or their ability to produce IL-10, indicating little, if any, impact of Treg cells on the generation and maintenance of Breg cells.

Conclusions

Our data indicate that increased Breg cells might be a major source of elevated IL-10 in CHB and represent a critical and independent regulatory force in the development of impaired anti-HBV immunity, consequently contributing to the pathogenesis of CHB.

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Authors and Affiliations

  1. Institution for Laboratory Medicine, Changshu, China

    Yanping Gong, Meifang Wang, Guoqiang Zhou, Fu Han, Yanhong Cui, Jianping Qian, Hongxing Zhang, Huaimin Xiong, Jianhua Sheng & Tingwang Jiang

  2. Department of Infectious Diseases, No.2 People’s Hospital, Changshu, 215500, China

    Chao Zhao

  3. Department of Infectious Diseases, Bejing 302 Hospital, Bejing, 100039, China

    Peng Zhao

Authors
  1. Yanping Gong
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  2. Chao Zhao
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  3. Peng Zhao
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  4. Meifang Wang
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  5. Guoqiang Zhou
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  6. Fu Han
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  7. Yanhong Cui
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  10. Huaimin Xiong
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  11. Jianhua Sheng
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Corresponding author

Correspondence to Tingwang Jiang.

Additional information

Yanping Gong, Chao Zhao and Peng Zhao have contributed equally to this work.

Electronic supplementary material

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10620_2014_3358_MOESM1_ESM.jpg

Supplementary Fig. 1. Depletion of Treg cells by the administration of denileukin diftitox. To deplete Treg cells, isolated PBMCs from 10 patients with CHB were cultured for 18 to 20 h in RPMI-1640 complete medium with denileukin diftitox (2-4 nM), washed, and replated in complete media for 1 day to allow recovery for further analysis. The outcome of Treg depletion was verified by flow cytometry. A. A representative analysis of Treg before and after denileukin diftitox treatment is shown. B. Treg cells were effectively depleted after denileukin diftitox treatment in PBMCs of 10 patients with CHB. (JPEG 95 kb)

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Gong, Y., Zhao, C., Zhao, P. et al. Role of IL-10-Producing Regulatory B Cells in Chronic Hepatitis B Virus Infection. Dig Dis Sci 60, 1308–1314 (2015). https://doi.org/10.1007/s10620-014-3358-1

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  • DOI: https://doi.org/10.1007/s10620-014-3358-1

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