Interleukin (IL)-35 is an inhibitory cytokine consisting of IL-12A and Epstein-Barr virus-induced gene 3 (Ebi3) and is required by regulatory T-cells (Tregs) for maximal activity. During chronic hepatitis B virus (HBV) infection, Tregs have immunosuppressive effects on HBV-specific T helper (Th) cells, yet little is known about the complex regulation of Tregs and their contribution to the inadequate immune system response to the virus. In the present study, we investigated whether IL-35 is involved in HBV-related cellular immune responses. Cluster of differentiation (CD)4+ T-cells from peripheral blood were derived from healthy volunteers, resolved HBV individuals and chronic active hepatitis B patients and stimulated with CD3/28-conjugated beads. We analysed mRNA and protein levels of IL-35 and assessed the inhibitory effect of IL-35 on HBV core antigen-specific cytotoxic T lymphocytes (CTLs), dendritic cells (DCs) and effector T-cells (Teffs). Correlation analyses between liver inflammation and HBV DNA load were conducted. Results show that chronic HBV patients harbour significantly higher levels of Ebi3 mRNA and protein in CD4+ T-cells compared with healthy volunteers and resolved HBV individuals. IL-35 suppressed the proliferation of HBV antigen-specific CTLs and interferon (IFN)-γ production in vitro. Ex vivo, IL-35 decreased the proliferation of CD4+CD45RA+ naïve T-cells, especially in CD4+CD25−CD45RA+ naïve Teffs. IL-35 inhibited the expansion of CD11c+ DCs. Our data indicate that IL-35 is highly expressed in chronic HBV CD4+ T-cells and plays an important role in the inhibition of the cellular immune response in chronic HBV.
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Research Article|
June 11 2015
IL-35 inhibits HBV antigen-specific IFN-γ-producing CTLs in vitro
Xuefen Li;
Xuefen Li
1
*State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, PR China
†Department of Laboratory Medicine, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, PR China
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Li Tian;
Li Tian
1
*State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, PR China
†Department of Laboratory Medicine, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, PR China
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Yuejiao Dong;
Yuejiao Dong
†Department of Laboratory Medicine, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, PR China
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Qiaoyun Zhu;
Qiaoyun Zhu
*State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, PR China
†Department of Laboratory Medicine, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, PR China
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Yiyin Wang;
Yiyin Wang
†Department of Laboratory Medicine, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, PR China
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Wenzheng Han;
Wenzheng Han
†Department of Laboratory Medicine, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, PR China
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Xia Liu;
Xia Liu
*State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, PR China
†Department of Laboratory Medicine, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, PR China
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Qin Ni;
Qin Ni
*State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, PR China
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Yu Chen;
*State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, PR China
†Department of Laboratory Medicine, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, PR China
Correspondence: Dr Yu Chen (email zychenyu@126.com) or Dr Lanjuan Li (email ljli@zju.edu.cn).
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Lanjuan Li
*State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, PR China
Correspondence: Dr Yu Chen (email zychenyu@126.com) or Dr Lanjuan Li (email ljli@zju.edu.cn).
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Publisher: Portland Press Ltd
Received:
August 26 2014
Revision Received:
March 18 2015
Accepted:
April 14 2015
Accepted Manuscript online:
April 14 2015
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2015 Authors; published by Portland Press Limited
2015
Clin Sci (Lond) (2015) 129 (5): 395–404.
Article history
Received:
August 26 2014
Revision Received:
March 18 2015
Accepted:
April 14 2015
Accepted Manuscript online:
April 14 2015
Citation
Xuefen Li, Li Tian, Yuejiao Dong, Qiaoyun Zhu, Yiyin Wang, Wenzheng Han, Xia Liu, Qin Ni, Yu Chen, Lanjuan Li; IL-35 inhibits HBV antigen-specific IFN-γ-producing CTLs in vitro. Clin Sci (Lond) 1 September 2015; 129 (5): 395–404. doi: https://doi.org/10.1042/CS20140511
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