Chronic hepatitis C viral infection reduces NK cell frequency and suppresses cytokine secretion: Reversion by anti-viral treatment.
Impaired activity of NK (natural killer) cells has been proposed as a mechanism contributing to viral persistence and chronic infection in hepatitis C (HCV) infection. We aimed to assess the impact of HCV infection on NK cells regarding frequency, subset distribution, and cytotoxic and cytokine secretion functions, as well as IFN-alpha and ribavirin therapeutic effects on NK cells. Significant reduction of total NK frequency and the CD56(dim)16(+) subset was observed in chronic HCV patients. IFN-gamma expression upon stimulation with K562 was severely suppressed but cytotoxicity measured by CD107a expression was maintained. These adverse effects were reversed after treatment with pegylated IFN-alpha and ribavirin; however, these skewed functions were not recovered in treatment-resistant patients. Thus, HCV chronic infection severely affects NK functions, except for cytotoxicity. Altered NK cell frequency and cytokine secretion by HCV infection may contribute to impaired cellular immune response and virus persistence.
Center for AIDS Research, Kumamoto University, Japan.
Omar
O
Dessouki
Yasuyuki
Y
Kamiya
Hiroyasu
H
Nagahama
Motohiko
M
Tanaka
Shinya
S
Suzu
Yutaka
Y
Sasaki
Seiji
S
Okada
D023181:Antimicrobial Cationic Peptides; D000998:Antiviral Agents / Q000627:therapeutic use; D015550:Cell Degranulation; D016207:Cytokines / Q000378:metabolism*; D016174:Hepacivirus / Q000276:immunology* / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D018655:Lymphocyte Count; D010455:Peptides / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D012367:RNA, Viral; D011994:Recombinant Proteins; D012008:Recurrence; D012254:Ribavirin / Q000627:therapeutic use*
D023181:Antimicrobial Cationic Peptides; D000998:Antiviral Agents; D016207:Cytokines; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D010455:Peptides; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C026530:myroridin K; C100416:peginterferon alfa-2a