HBcAg induces interleukin-10 production, inhibiting HBcAg-specific Th17 responses in chronic hepatitis B patients.
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.
Li
Jie
J
State Key Laboratory of Infectious Disease Diagnosis and Treatment, First Affiliated Hospital, Zhejiang University College of Medicine, Zhejiang, PR China.
Wu
Wei
W
Peng
Guoping
G
Chen
Feng
F
Bai
Minghui
M
Zheng
Min
M
Chen
Zhi
Z
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
D019138:Antibodies, Blocking; D006512:Hepatitis B Core Antigens; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D011994:Recombinant Proteins; D016753:Interleukin-10