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Author Notes:

Helmut M. Diepolder: hdiepold@med.uni-muenchen.de

Conceived and designed the experiments: RP ML PK HD AU GP.

Performed the experiments: ML RT PK AU KP MH SG AR HN MO AH.

Analyzed the data: ML RT NS TS CD HD TB AU KP SG NG MJ GP HN MO AH WS.

Contributed reagents/materials/analysis tools: RP PK JW NS SF TS CD TB NG MJ RZ TS TG WS.

Wrote the paper; Conceived and designed the study; Enrolled patients; Wrote the first draft of the paper: HD.

Contributed equally: ML and AU

See Publication for full list of authors.

The authors would like to thank the patients and clinicians involved in this study.

The authors have declared that no competing interests exist.

Subjects:

Research Funding:

This work was supported by funding from the Wellcome Trust, the James Martin School of the 21st Century, Oxford and the Kompetenznetz Hepatitis HepNet (Teilprojekt 10.2.1).

This work is part of the activities of the VIRGIL European Network of Excellence on Antiviral Drug Resistance supported by a grant (LSHM-CT-2004-503359) from the Priority 1 “Life Sciences, Genomics and Biotechnology for Health” programme in the 6th Framework Programme of the EU.

Keywords:

  • Science & Technology
  • Multidisciplinary Sciences
  • Science & Technology - Other Topics

Tracking Virus-Specific CD4+T Cells during and after Acute Hepatitis C Virus Infection

Tools:

Journal Title:

PLoS ONE

Volume:

Volume 2, Number 7

Publisher:

, Pages e649-e649

Type of Work:

Article | Final Publisher PDF

Abstract:

Background. CD4+ T cell help is critical in maintaining antiviral immune responses and such help has been shown to be sustained in acute resolving hepatitis C. In contrast, in evolving chronic hepatitis C CD4+ T cell helper responses appear to be absent or short-lived, using functional assays. Methodology/Prencipal Findings. Here we used a novel HLA-DR1 tetramer containing a highly targeted CD4+ T cell epitope from the hepatitis C virus non-structural protein 4 to track number and phenotype of hepatitis C virus specific CD4+ T cells in a cohort of seven HLA-DR1 positive patients with acute hepatitis C in comparison to patients with chronic or resolved hepatitis C. We observed peptide-specific T cells in all seven patients with acute hepatitis C regardless of outcome at frequencies up to 0.65% of CD4+ T cells. Among patients who transiently controlled virus replication we observed loss of function, and/or physical deletion of tetramer+ CD4+ T cells before viral recrudescence. In some patients with chronic hepatitis C very low numbers of tetramer+ cells were detectable in peripheral blood, compared to robust responses detected in spontaneous resolvers. Importantly we did not observe escape mutations in this key CD4+ T cell epitope in patients with evolving chronic hepatitis C. Conclusions/Significance. During acute hepatitis C a CD4+ T cell response against this epitope is readily induced in most, if not all, HLA-DR1 + patients. This antiviral T cell population becomes functionally impaired or is deleted early in the course of disease in those where viremia persists.

Copyright information:

© 2007 Lucas et al.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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