Kennedy, P.; (2007) Stimulation requirement and pathogenetic significance of T cells during chronic viral hepatitis. Doctoral thesis , University of London.

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Abstract

Hepatitis B virus (HBV) and Hepatitis C virus (HCV) are important causes of liver inflammation and fibrosis. More than 500 million people are persistently infected worldwide and consequently are at increased risk of developing chronic liver disease, cirrhosis and hepatocellular carcinoma. Both viruses share some similarities however, disease severity varies greatly from subject to subject and the variation in clinical course is a hallmark of viral hepatitis. The failure of the immune system to prevent persistent infection and chronic necroinflammatory change is central to understanding the disease caused by these human viruses. The Introduction to this Thesis reviews our current understanding of the immunopathogenesis and natural history of both viruses in the context of the clinical and scientific challenge that chronic viral hepatitis represents. The body of this work was to focus on immunological events which might shape and possibly dictate disease outcome in viral hepatitis. In this thesis I set out to investigate areas of cellular immunity which may contribute to pathology or protection in HBV and HCV. I have focused on the impact of cross-reactive T cells activated by HCV peptides and report that this may constitute a common occurrence in human viral infections. I explore the role of the NK cell receptor, NKG2D, in the modulation of CD8+T cell response in type B and C chronic viral hepatitis and report the impact of this novel receptor in human liver disease for the first time.

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