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Title

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

Authors
Schulze Zur Wiesch, Julian
Lewis-Ximenez, Lia
Kasprowicz, Victoria
Nolan, Brian E
Streeck, Hendrik
Aneja, Jasneet
Reyor, Laura L
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Published in Journal of Experimental Medicine. 2012, vol. 209, no. 1, p. 61-75
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 AdultAntibodies, Neutralizing/immunologyAntiviral Agents/therapeutic useCD4-Positive T-Lymphocytes/drug effects/immunologyCell Proliferation/drug effectsCohort StudiesEpitopes, T-Lymphocyte/immunologyFemaleHepacivirus/immunologyHepatitis C/drug therapy/immunology/virologyHistocompatibility Antigens Class II/immunologyHumansInterleukin-2/immunology/pharmacologyLymphocyte Activation/drug effects/immunologyMaleMiddle AgedRemission, SpontaneousViremia/immunologyYoung Adult
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PMID: 22213804
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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: Journal of Experimental Medicine, 2012, vol. 209, n° 1, p. 61-75. https://archive-ouverte.unige.ch/unige:27590

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Deposited on : 2013-04-26

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