en
Scientific article
English

Broadly directed virus-specific CD4+ T cell responses are primed during acute hepatitis C infection, but rapidly disappear from human blood with viral persistence

Published inThe Journal of experimental medicine, vol. 209, no. 1, p. 61-75
Publication date2012
Abstract

Vigorous proliferative CD4(+) T cell responses are the hallmark of spontaneous clearance of acute hepatitis C virus (HCV) infection, whereas comparable responses are absent in chronically evolving infection. Here, we comprehensively characterized the breadth, specificity, and quality of the HCV-specific CD4(+) T cell response in 31 patients with acute HCV infection and varying clinical outcomes. We analyzed in vitro T cell expansion in the presence of interleukin-2, and ex vivo staining with HCV peptide-loaded MHC class II tetramers. Surprisingly, broadly directed HCV-specific CD4(+) T cell responses were universally detectable at early stages of infection, regardless of the clinical outcome. However, persistent viremia was associated with early proliferative defects of the HCV-specific CD4(+) T cells, followed by rapid deletion of the HCV-specific response. Only early initiation of antiviral therapy was able to preserve CD4(+) T cell responses in acute, chronically evolving infection. Our results challenge the paradigm that HCV persistence is the result of a failure to prime HCV-specific CD4(+) T cells. Instead, broadly directed HCV-specific CD4(+) T cell responses are usually generated, but rapid exhaustion and deletion of these cells occurs in the majority of patients. The data further suggest a short window of opportunity to prevent the loss of CD4(+) T cell responses through antiviral therapy.

Keywords
  • Adult
  • Antibodies, Neutralizing/immunology
  • Antiviral Agents/therapeutic use
  • CD4-Positive T-Lymphocytes/drug effects/immunology
  • Cell Proliferation/drug effects
  • Cohort Studies
  • Epitopes, T-Lymphocyte/immunology
  • Female
  • Hepacivirus/immunology
  • Hepatitis C/drug therapy/immunology/virology
  • Histocompatibility Antigens Class II/immunology
  • Humans
  • Interleukin-2/immunology/pharmacology
  • Lymphocyte Activation/drug effects/immunology
  • Male
  • Middle Aged
  • Remission, Spontaneous
  • Viremia/immunology
  • Young Adult
Affiliation Not a UNIGE publication
Citation (ISO format)
SCHULZE ZUR WIESCH, Julian et al. Broadly directed virus-specific CD4+ T cell responses are primed during acute hepatitis C infection, but rapidly disappear from human blood with viral persistence. In: The Journal of experimental medicine, 2012, vol. 209, n° 1, p. 61–75. doi: 10.1084/jem.20100388
Main files (1)
Article (Published version)
accessLevelRestricted
Identifiers
ISSN of the journal0022-1007
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