title: Heterologous T cell immunity in severe hepatitis C virus infection.
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. 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.
authors.affiliation: Laboratory of Viral Immunopathology, Department of Infectious Diseases and Hepatology, Azienda Ospedaliera Universitaria di Parma, Parma 43100, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Urbani
authors.forename: Barbara
authors.initials: B
authors.lastname: Amadei
authors.forename: Paola
authors.initials: P
authors.lastname: Fisicaro
authors.forename: Massimo
authors.initials: M
authors.lastname: Pilli
authors.forename: Gabriele
authors.initials: G
authors.lastname: Missale
authors.forename: Antonio
authors.initials: A
authors.lastname: Bertoletti
authors.forename: Carlo
authors.initials: C
authors.lastname: Ferrari
mesh_terms: D000208:Acute Disease; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D003429:Cross Reactions / Q000276:immunology; D005260:Female; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007700:Kinetics; D008297:Male
chemical_list: D007371:Interferon-gamma