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Publication Detail
IL-10-producing regulatory B cells in the pathogenesis of chronic hepatitis B virus infection.
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Journal Article
  • Authors:
    Das A, Ellis G, Pallant C, Lopes AR, Khanna P, Peppa D, Chen A, Blair P, Dusheiko G, Gill U, Kennedy PT, Brunetto M, Lampertico P, Mauri C, Maini MK
  • Publication date:
    15/10/2012
  • Pagination:
    3925, 3935
  • Journal:
    J Immunol
  • Volume:
    189
  • Issue:
    8
  • Status:
    Published
  • Country:
    United States
  • PII:
    jimmunol.1103139
  • Language:
    eng
  • Keywords:
    Adult, Aged, B-Lymphocyte Subsets, B-Lymphocytes, Regulatory, CD8-Positive T-Lymphocytes, Cell Differentiation, Cells, Cultured, Female, Hepatitis B virus, Hepatitis B, Chronic, Humans, Interleukin-10, Longitudinal Studies, Male, Middle Aged, Young Adult
Abstract
A regulatory subset of B cells has been found to modulate immune responses in autoimmunity, infection, and cancer, but it has not been investigated in the setting of human persistent viral infection. IL-10 is elevated in patients with chronic hepatitis B virus infection (CHB), but its cellular sources and impact on antiviral T cells have not been addressed. We investigated the role of IL-10 and regulatory B cells in the pathogenesis of CHB. Serum IL-10 levels were studied longitudinally in patients with CHB undergoing spontaneous disease flares. There was a close temporal correlation between IL-10 levels and fluctuations in viral load or liver inflammation. Blockade of IL-10 in vitro rescued polyfunctional virus-specific CD8 T cell responses. To investigate the potential contribution of regulatory B cells, their frequency was measured directly ex vivo and after exposure to stimuli relevant to hepatitis B virus (HBV) (CpG or HBV Ags). IL-10-producing B cells were enriched in patients, and their frequency correlated temporally with hepatic flares, both after stimulation and directly ex vivo. Phenotypically, these cells were predominantly immature (CD19(+)CD24(hi)CD38(hi)) ex vivo; sorted CD19(+)CD24(hi)CD38(hi) cells suppressed HBV-specific CD8 T cell responses in an IL-10-dependent manner. In summary, these data reveal a novel IL-10-producing subset of B cells able to regulate T cell immunity in CHB.
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Div of Medicine
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Div of Infection & Immunity
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Div of Infection & Immunity
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Div of Infection & Immunity
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