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

• Authors: Michaela Lucas, University of Oxford; Axel Ulsenheimer, University of Munich; Katja Pfafferot, Royal Perth Hospital; Malte H.J. Heeg, University of Munich; Silvana Gaudieri, Royal Perth Hospital; Norbert Gruener, University of Munich; Andri Rauch, Royal Perth Hospital; Cheryl Day, Emory University
• Journal Title: PLoS ONE
• Volume: Volume 2, Number 7
• Publisher: Public Library of Science | 2007-07-25, Pages e649-e649
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1371/journal.pone.0000649
• Subjects: Health Sciences, Immunology; Biology, Biostatistics
• Keywords: Science & Technology; Multidisciplinary Sciences; Science & Technology - Other Topics

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.