Comparison of immune restoration in early versus late alpha interferon therapy against hepatitis C virus.
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.
Abdel-Hakeem
Mohamed S
MS
Centre de Recherche du CHUM, Hôpital St-Luc, Montréal, Québec, Canada.
Bédard
Nathalie
N
Badr
Gamal
G
Ostrowski
Mario
M
Sékaly
Rafick P
RP
Bruneau
Julie
J
Willems
Bernard
B
Heathcote
E Jenny
EJ
Shoukry
Naglaa H
NH
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
D000998:Antiviral Agents; C508594:IL2 protein, human; D007370:Interferon Type I; D007376:Interleukin-2; D012367:RNA, Viral; D011994:Recombinant Proteins; D007371:Interferon-gamma