Tracking virus-specific CD4+ T cells during and after acute hepatitis C virus infection.

Journal article

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/PRINCIPAL 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.

Authors: Lucas, M; Ulsenheimer, A; Pfafferot, K; Heeg, M; Gaudieri, S

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Public Library of Science
• Journal: PloS one
• Volume: 2
• Issue: 7
• Article number: e649
• Publication date: 2007-01-01
• DOI: 10.1371/journal.pone.0000649
• EISSN: 1932-6203
• ISSN: 1932-6203
• Language: English
• Keywords: Viral Proteins; Hepatitis C; Acute Disease; Reverse Transcriptase Polymerase Chain Reaction; Immunity, Cellular; Peptide Fragments; DNA Primers; Amino Acid Sequence; Male; CD4-Positive T-Lymphocytes; Hepacivirus; Genotype; Base Sequence; Epitopes, T-Lymphocyte; HLA-DR1 Antigen; T-Lymphocytes, Helper-Inducer; Humans; Liver; Female