Hepatitis C virus core protein impairs in vitro priming of specific T cell responses by dendritic cells and hepatocytes

Mona Zimmermann, Christin Flechsig, Nicola La Monica, Marco Tripodi, Guido Adler, Nektarios Dikopoulos

Research output: Contribution to journalArticle

Abstract

Background/Aims: Hepatitis C virus leads to chronic hepatitis in the majority of infected individuals. The mechanism of viral persistence is not completely understood. Hepatitis C virus core protein is produced within hepatocytes and is secreted during HCV infection. Our study characterizes the effects of core protein on T cell priming in mice. Methods: We used a system of antigen-specific in vitro priming of CD4+ and CD8+ T cells by myeloid dendritic cells, hepatoma cells or primary hepatocytes. Core protein was either added to the cultures or expressed by antigen-presenting cells. Results: Antigen-presenting cells treated with core protein showed reduced surface expression of major histocompatibility molecules. Myeloid dendritic cells showed also reduced expression of costimulatory molecules. CD4+ and CD8+ T cells primed by these cells showed defects in activation, proliferation, and cytokine production. Importantly, CD4+ and also CD8+ T cells primed in the presence of core protein showed an increase in interleukin-10 production resembling the phenotype of regulatory T cells. Conclusions: Hepatitis C virus core protein inhibits priming of antigen-specific CD4+ and CD8+ T cell responses by downregulation of major histocompatibility molecules and costimulatory molecules on antigen-presenting cells and induces development of IL-10-producing T cells.

Original languageEnglish
Pages (from-to)51-60
Number of pages10
JournalJournal of Hepatology
Volume48
Issue number1
DOIs
Publication statusPublished - Jan 2008

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Keywords

  • Core protein
  • Costimulatory molecules
  • Hepatitis C virus
  • Hepatocytes
  • MHC class I molecules
  • Myeloid dendritic cells
  • Regulatory T cells
  • T cell priming

ASJC Scopus subject areas

  • Gastroenterology

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