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Original Article

^a Nuffield Department of Clinical Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, United Kingdom
^b Medical Research Council Human Immunology Unit, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, United Kingdom
^c Infectious Disease Unit and AIDS Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02129
^d Gastrointestinal Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02129
Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital, Level 7, Oxford OX3 9DU, UK.44-1865-22099344-1865-221349

klerner{at}molbiol.ox.ac.uk

Although hepatitis C virus (HCV) infection is very common, identification of patients during acute infection is rare. Consequently, little is known about the immune response during this critical stage of the disease. We analyzed the T lymphocyte response during and after acute resolving HCV infection in three persons, using interferon (IFN)- enzyme-linked immunospot (ELISPOT) and human histocompatibility leukocyte antigen (HLA) peptide tetramer assays. Acute infection was associated with a broadly directed T helper and cytotoxic T lymphocyte (CTL) response, which persisted after resolution of clinical hepatitis and clearance of viremia. At the earliest time point studied, highly activated CTL populations were observed that temporarily failed to secrete IFN-, a "stunned" phenotype, from which they recovered as viremia declined. In long-term HCV-seropositive persons, CTL responses were more common in persons who had cleared viremia compared with those with persistent viremia, although the frequencies of HCV-specific CTLs were lower than those found in persons during and after resolution of acute HCV infection. These studies demonstrate a strong and persistent CTL response in resolving acute HCV infection, and provide rationale to explore immune augmentation as a therapeutic intervention in chronic HCV infection.

Key Words: acute infection • cytotoxic T lymphocytes • T helper cells • tetramer staining • interferon

Address correspondence to Bruce Walker, Infectious Disease Unit and AIDS Research Center, Massachusetts General Hospital, 149 13th St., Charlestown, MA 02129. Phone: 617-724-8332; Fax: 617-726-7416; E-mail: bwalker{at}helix.mgh.harvard.edu

Abbreviations used in this paper: aa, amino acid(s); ALT, alanine transaminase; B-LCL, B lymphoblastoid cell line; CCR, CC chemokine receptor; ELISPOT, enzyme-linked immunospot; HCV, hepatitis C virus; PerCP, peridinine chlorophyll protein; RT, reverse transcription; SOD, superoxide dismutase.

© 2000 The Rockefeller University Press

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This article has been cited by other articles:

• Welsh, R. M. (2001). Assessing Cd8 T Cell Number and Dysfunction in the Presence of Antigen. JEM 193: f19-f22 [Full Text]  

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