title: HBcAg induces interleukin-10 production, inhibiting HBcAg-specific Th17 responses in chronic hepatitis B patients.
abstract: T-helper (Th) 17 cells have been shown to have an important role in host defense against viral infection. However, little is known about the regulation of Th17 cells in hepatitis B virus (HBV) infections. Peripheral blood mononuclear cells (PBMCs) isolated from patients with chronic hepatitis B (CHB) were stimulated with anti-interleukin (IL)-10 antibody or recombinant IL-10. The frequency of hepatitis B core antigen (HBcAg)-specific Th17 cells was characterized and produced cytokines were determined by flow cytometry. A low frequency of Th17 cells and a high frequency of Th1 cells were detected in CHB patients. HBcAg stimulation promoted IL-17A, IL-22, IL-23, IL-6, transforming growth factor (TGF)-β and IL-10 production by PBMCs from CHB patients, but not from healthy controls. Furthermore, endogenous IL-10 inhibited HBcAg-stimulated production of IL-17A, IL-22, IL-6 and IL-23, but not TGF-β. Treatment with IL-10 inhibited the HBcAg-stimulated activation of Th17 cells, whereas anti-IL-10 antibody significantly increased the frequency of Th17 and Th1 cells, but not that of CD4(+)CD25(+) regulatory T cells, associated with upregulating RORγt expression in CD4(+) T cells. HBcAg stimulated the production of IL-10, which negatively regulated HBcAg-specific Th17 cell responses in CHB patients. Our findings may represent one evasion strategy for HBV to subvert specific antiviral responses in humans.
authors.affiliation: State Key Laboratory of Infectious Disease Diagnosis and Treatment, First Affiliated Hospital, Zhejiang University College of Medicine, Zhejiang, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.forename: Guoping
authors.initials: G
authors.lastname: Peng
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.forename: Minghui
authors.initials: M
authors.lastname: Bai
authors.forename: Min
authors.initials: M
authors.lastname: Zheng
authors.forename: Zhi
authors.initials: Z
authors.lastname: Chen
mesh_terms: D019138:Antibodies, Blocking / Q000494:pharmacology; D048708:Cell Growth Processes / Q000187:drug effects; D002469:Cell Separation; D002478:Cells, Cultured; D005434:Flow Cytometry; D006512:Hepatitis B Core Antigens / Q000276:immunology / Q000378:metabolism*; D006515:Hepatitis B virus / Q000276:immunology* / Q000472:pathogenicity; D019694:Hepatitis B, Chronic / Q000276:immunology* / Q000821:virology; D006801:Humans; D057131:Immune Evasion; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000821:virology
chemical_list: D019138:Antibodies, Blocking; D006512:Hepatitis B Core Antigens; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D011994:Recombinant Proteins; D016753:Interleukin-10