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Cellular immune responses against persistent hepatitis C virus: gone but not forgotten
  1. P Klenerman,
  2. N Semmo
  1. Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK
  1. Correspondence to:
    Dr P Klenerman
    Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford OX3 9TU, UK; paul.klenerman{at}

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Failure to sustain antiviral T cell responses is a hallmark of persistent hepatitis C virus infection. Early loss of T cell proliferative capacity after acute disease appears to be an important component of this process. T cell function may, however, be restored in vitro with interleukin 2

Although the prevalence of persistent hepatitis C virus (HCV) infection is very high, acute HCV infection is rarely encountered by most clinicians. The reasons for this include often a relatively mild presentation, as well as failure to seek medical attention. Nevertheless, analysis of the events which occur during and following acute HCV infection is very important in trying to disentangle why some infections persist and others are cleared—defining so-called “correlates of protection”. Thus immunological studies of acute HCV are on the one hand potentially extremely informative and on the other very difficult to do.

Acute infection may be followed by rapid clearance or—in the majority of cases—lifelong persistence, often preceded by a period of partial control. Over the past decade a substantial amount of data have been generated pointing to a crucial role for cellular immune responses in determining these outcomes.1 There is no doubt that a number of factors, including innate responses and neutralising antibody responses, all contribute to host resistance to infection. However, the difficulty in analysing strain specific neutralising antibodies and the great variability in HCV envelope (the target of such antibodies) means that much attention has focused on T cell immunity. The hope is that by reproducing T cell immune responses associated with successful outcomes it might be possible to generate successful vaccines for protection or immune based therapy.

Previous studies of cellular immune responses during and after acute HCV infection have demonstrated the following general features:

  • CD4+ T cell responses—notably proliferative responses—may be observed in acute infection …

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