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

Lucas, Michaela; Ulsenheimer, Axel; Pfafferot, Katja; Heeg, Malte H J; Gaudieri, Silvana; Grüner, Norbert; Rauch, Andri; Gerlach, J Tilman; Jung, Maria-Christina; Zachoval, Reinhart; Pape, Gerd R; Schraut, Winfried; Santantonio, Teresa; Nitschko, Hans; Obermeier, Martin; Phillips, Rodney; Scriba, Thomas J; Semmo, Nasser; Day, Cheryl; Weber, Jonathan N; ... (2007). Tracking virus-specific CD4+ T cells during and after acute hepatitis C virus infection. PLoS ONE, 2(7), e649. Lawrence, Kans.: Public Library of Science 10.1371/journal.pone.0000649

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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.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Infectiology
UniBE Contributor:	Rauch, Andri
ISSN:	1932-6203
ISBN:	17653276
Publisher:	Public Library of Science
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 14:59
Last Modified:	05 Dec 2022 14:18
Publisher DOI:	10.1371/journal.pone.0000649
PubMed ID:	17653276
Web of Science ID:	000207452200018
URI:	https://boris.unibe.ch/id/eprint/25695 (FactScience: 60731)