Peripheral virus-specific T-cell interleukin-10 responses develop early in acute hepatitis C infection and become dominant in chronic hepatitis

David E. Kaplan, Fusao Ikeda, Yun Li, Nobuhiro Nakamoto, Sutharsan Ganesan, Mary E. Valiga, Frederick A. Nunes, K. Rajender Reddy, Kyong Mi Chang

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Background /Aims: Interleukin-10 (IL-10) has been ascribed pro-viral but anti-fibrotic properties in chronic hepatitis C virus (HCV) infection. In this study, we examined the role of HCV-specific T-cell IL-10 response in patients with acute and chronic HCV infection. Methods: Peripheral HCV-specific T-cell IL-10 and IFNγ responses were measured in cytokine Elispot assay using overlapping HCV-derived peptides in patients with chronic (n = 61), resolved (n = 15) and acute (n = 8) hepatitis C, looking for their onset, quantity, breadth and durability relative to clinical and virological outcomes. The source and effect of HCV-specific IL-10 response were determined in depletion and IL-10 neutralization experiments. Results: Both HCV-specific IL-10 and IFNγ responses were detected early within 1-2 months of acute clinical hepatitis C. However, only HCV-specific IL-10 response correlated with elevated liver enzymes, increased viremia and suppressed HCV-specific CD4+ T-cell proliferation in acute infection. While these associations were lost in established chronic infection, HCV-specific IL-10 responses were increased in patients without cirrhosis while IL-10 blockade enhanced antiviral effector IFNγ responses. Conclusions: HCV-specific IL-10 Tr1 responses may play a dual role in HCV infection, dampening effector T-cells to promote viral persistence in acute infection but also protecting against progressive fibrosis in chronic infection.

Original languageEnglish
Pages (from-to)903-913
Number of pages11
JournalJournal of Hepatology
Volume48
Issue number6
DOIs
Publication statusPublished - 2008 Jun 1
Externally publishedYes

Keywords

  • CD8 T-cells
  • HCV
  • Hepatitis C
  • IL-10
  • Interferon-gamma
  • Interleukin-10
  • Regulatory T-cells

ASJC Scopus subject areas

  • Hepatology

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