title: Comparison of immune restoration in early versus late alpha interferon therapy against hepatitis C virus.
abstract: Early alpha interferon (IFN-alpha) therapy against hepatitis C virus (HCV) rescues polyfunctional, virus-specific memory CD8(+) T cells, but whether immune restoration is possible during late therapy remains controversial. We compared immune restoration of HCV-specific memory T cells in patients who cleared HCV infection spontaneously and following early or late IFN therapy. Multifunctional CD4(+) and CD8(+) memory T cells were detected in spontaneous resolvers and in individuals treated early following an acute infection. In contrast, limited responses were detected in patients treated during chronic infection, and the phenotype of HCV-specific cells was influenced by autologous viral sequences. Our data suggest that irreversible damage to the HCV-specific memory T-cell response is associated with chronic HCV infection.
authors.affiliation: Centre de Recherche du CHUM, Hôpital St-Luc, Montréal, Québec, Canada.
authors.forename: Mohamed S
authors.initials: MS
authors.lastname: Abdel-Hakeem
authors.forename: Nathalie
authors.initials: N
authors.lastname: Bédard
authors.forename: Gamal
authors.initials: G
authors.lastname: Badr
authors.forename: Mario
authors.initials: M
authors.lastname: Ostrowski
authors.forename: Rafick P
authors.initials: RP
authors.lastname: Sékaly
authors.forename: Julie
authors.initials: J
authors.lastname: Bruneau
authors.forename: Bernard
authors.initials: B
authors.lastname: Willems
authors.forename: E Jenny
authors.initials: EJ
authors.lastname: Heathcote
authors.forename: Naglaa H
authors.initials: NH
authors.lastname: Shoukry
mesh_terms: D000208:Acute Disease; D000998:Antiviral Agents / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015550:Cell Degranulation / Q000276:immunology; D015331:Cohort Studies; D016174:Hepacivirus / Q000276:immunology; D006526:Hepatitis C / Q000276:immunology* / Q000628:therapy* / Q000821:virology; D019698:Hepatitis C, Chronic / Q000276:immunology* / Q000628:therapy* / Q000821:virology; D006801:Humans; D007156:Immunologic Memory; D007370:Interferon Type I / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D008969:Molecular Sequence Data; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D013997:Time Factors
chemical_list: D000998:Antiviral Agents; C508594:IL2 protein, human; D007370:Interferon Type I; D007376:Interleukin-2; D012367:RNA, Viral; D011994:Recombinant Proteins; D007371:Interferon-gamma