Published 7 March 2005. doi:10.1084/jem.20041058
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 201, Number 5, 675-680
Heterologous T cell immunity in severe hepatitis C virus infection
Simona Urbani1,
Barbara Amadei1,
Paola Fisicaro1,
Massimo Pilli1,
Gabriele Missale1,
Antonio Bertoletti2,3, and
Carlo Ferrari1
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
CORRESPONDENCE Carlo Ferrari: cafer{at}tin.it
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.
Abbreviations used: ALT, alanine aminotransferase; HCV, hepatitis C virus; SFC, spot-forming cell.
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