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World J Gastroenterol. Sep 28, 2007; 13(36): 4831-4838
Published online Sep 28, 2007. doi: 10.3748/wjg.v13.i36.4831
CD4+ T cell responses in hepatitis C virus infection
Nasser Semmo, Paul Klenerman
Nasser Semmo, Department of Medicine II, University Hospital Freiburg, Hugstetter Strasse 55, 79106 Freiburg, Germany
Paul Klenerman, Nuffield Department of Clinical Medicine, University of Oxford, The Peter Medawar Building for Pathogen Research, South Parks Road, Oxford OX1 3SY, United Kingdom
Author contributions: All authors contributed equally to the work.
Supported by the Deutsche Forschungsgemeinschaft and the Wellcome Trust and the James Martin School for the 21st century, Oxford
Correspondence to: Paul Klenerman, Nuffield Department of Clinical Medicine, University of Oxford, The Peter Medawar Building for Pathogen Research, South Parks Road, Oxford OX1 3SY, United Kingdom. paul.klenerman@medawar.ox.ac.uk
Telephone: +44-186-5281885 Fax: +44-186-5281236
Received: June 26, 2007
Revised: July 2, 2007
Accepted: July 9, 2007
Published online: September 28, 2007
Abstract

Hepatitis C virus (HCV) infection is a major cause of liver damage, with virus-induced end-stage disease such as liver cirrhosis and hepatocellular carcinoma resulting in a high rate of morbidity and mortality worldwide. Evidence that CD4+ T cell responses to HCV play an important role in the outcome of acute infection has been shown in several studies. However, the mechanisms behind viral persistence and the failure of CD4+ T cell responses to contain virus are poorly understood. During chronic HCV infection, HCV-specific CD4+ T cell responses are relatively weak or absent whereas in resolved infection these responses are vigorous and multispecific. Persons with a T-helper type I profile, which promotes cellular effector mechanisms are thought to be more likely to experience viral clearance, but the overall role of these cells in the immunopathogenesis of chronic liver disease is not known. To define this, much more data is required on the function and specificity of virus-specific CD4+ T cells, especially in the early phases of acute disease and in the liver during chronic infection. The role and possible mechanisms of action of CD4+ T cell responses in determining the outcome of acute and chronic HCV infection will be discussed in this review.

Keywords: Hepatitis C virus; CD4 T cells; HLA class II; Immune responses; Cytokines; Interleukin 2; Proliferation; Escape; Exhaustion