Heterologous T cell immunity in severe hepatitis C virus infection

Author:

Urbani Simona1,Amadei Barbara1,Fisicaro Paola1,Pilli Massimo1,Missale Gabriele1,Bertoletti Antonio23,Ferrari Carlo1

Affiliation:

1. Laboratory of Viral Immunopathology, Department of Infectious Diseases and Hepatology, Azienda Ospedaliera Universitaria di Parma, Parma 43100, Italy

2. Institute of Hepatology, University College of London, London WC1E 6HX, UK

3. Istituto Nazionale Malattie Infettive Lazzaro Spallanzani, 00149 Rome, Italy

Abstract

Hepatitis C virus (HCV) can cause liver disease of variable severity. Expansion of preexisting memory CD8 T cells by cross-reactivity with a new heterologous virus infection has been shown in mice to shape the repertoire of the primary response and to influence virus-related immunopathology (Selin, L.K. 2004. Immunity. 20:5–16). To determine whether this mechanism can influence the course of HCV infection, we analyzed the features of the HCV-specific CD8 T cell response in eight patients with acute HCV infection, two of whom had a particularly severe illness. Patients with severe hepatitis, but not those with mild disease, showed an extremely vigorous CD8 T cell response narrowly focused on a single epitope (NS3 1073–1081), which cross-reacted with an influenza neuraminidase sequence. Our results suggest that CD8 T cell cross-reactivity influences the severity of the HCV-associated liver pathology and depicts a model of disease induction that may apply to different viral infections.

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

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