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Discordant role of CD4 T-cell response relative to neutralizing antibody and CD8 T-cell responses in acute hepatitis C.

Kaplan, David E and Sugimoto, Kazushi and Newton, Kimberly and Valiga, Mary E and Ikeda, Fusao and Aytaman, Ayse and Nunes, Frederick A and Lucey, Michael R and Vance, Barbara A and Vonderheide, Robert H and Reddy, K Rajender and McKeating, Jane A and Chang, Kyong-Mi (2007) Discordant role of CD4 T-cell response relative to neutralizing antibody and CD8 T-cell responses in acute hepatitis C. Gastroenterology, 132 (2). pp. 654-66. ISSN 0016-5085

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Identification Number/DOI: http://dx.doi.org/10.1053/j.gastro.2006.11.044

BACKGROUND & AIMS: Acute hepatitis C virus (HCV) infection becomes chronic in the majority of patients. Although HCV-specific CD4 T-cell response is associated with HCV clearance, less is known about virus-specific CD8 T-cell or neutralizing antibody (nAb) responses and the role of CD4 help in their induction during acute infection. METHODS: HCV-specific CD4, CD8, and HCV pseudoparticle (HCVpp) nAb responses were monitored in acutely HCV-infected patients to define their relative contributions to viral clearance. RESULTS: Our results show that the outcome of acute hepatitis C is associated with a functional hierarchy in HCV-specific CD4 T-cell response and the scope of virus-specific, total T-cell interferon-gamma response. HCV-specific CD8 T-cell response was readily detectable in acutely HCV-infected patients regardless of virologic outcome or virus-specific CD4 T-cell response. In contrast, HCVpp-specific nAbs were readily detected in patients with chronic evolution and impaired virus-specific CD4 T-cell response but not in patients who cleared infection with robust virus-specific CD4 T-cell response. CONCLUSIONS: The outcome of acute hepatitis C is associated with efficient virus-specific CD4 T-cell response(s) without which HCV-specific CD8 T-cell and heterologous nAb responses may develop but fail to clear viremia. Furthermore, HCV-specific nAb responses may not be induced despite robust virus-specific CD4 T-cell response.

Type of Work:Article
Date:2007 (Publication)
School/Faculty:Schools (1998 to 2008) > School of Medicine
Department:Immunity and Infection
Subjects:R Medicine (General)
QR355 Virology
QR180 Immunology
QR Microbiology
Institution:University of Birmingham
Copyright Holders:the AGA Institute
ID Code:484
Refereed:YES
Local Holdings:
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