438 689

Cited 56 times in

Cell-to-cell contact with hepatitis C virus-infected cells reduces functional capacity of natural killer cells

 Joo Chun Yoon  ;  Jong-Baeck Lim  ;  Jeon Han Park  ;  Jae Myun Lee 
 JOURNAL OF VIROLOGY, Vol.85(23) : 12557-12569, 2011 
Journal Title
Issue Date
Carcinoma, Hepatocellular/immunology ; Carcinoma, Hepatocellular/metabolism ; Carcinoma, Hepatocellular/pathology ; Cell Communication* ; Cells, Cultured ; Cytotoxicity, Immunologic ; Flow Cytometry ; Hepacivirus/pathogenicity ; Hepatitis C, Chronic/immunology* ; Hepatitis C, Chronic/metabolism ; Hepatitis C, Chronic/virology* ; Hepatocytes/immunology* ; Hepatocytes/metabolism ; Humans ; Interferon-gamma/metabolism ; Killer Cells, Natural/immunology* ; Killer Cells, Natural/metabolism* ; Liver Neoplasms/immunology ; Liver Neoplasms/metabolism ; Liver Neoplasms/pathology ; Lymphocyte Activation ; NK Cell Lectin-Like Receptor Subfamily K ; Natural Cytotoxicity Triggering Receptor 3 ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism ; T-Lymphocytes/pathology ; Virion/immunology*
The distinct feature of hepatitis C virus (HCV) infection is a high incidence of chronicity. The reason for chronic HCV infection has been actively investigated, and impairment of innate and adaptive immune responses against HCV is proposed as a plausible cause. Whereas functional impairment of HCV-specific T cells is well characterized, the role and functional status of natural killer (NK) cells in each phase of HCV infection are still elusive. We therefore investigated whether direct interaction between NK cells and HCV-infected cells modulates NK cell function. HCV-permissive human hepatoma cell lines were infected with cell culture-generated HCV virions and cocultured with primary human NK cells. Cell-to-cell contact between NK cells and HCV-infected cells reduced NK cells' capacity to degranulate and lyse target cells, especially in the CD56(dim) NK cell subset, which is characterized by low-density surface expression of CD56. The decrease in degranulation capacity was correlated with downregulated expression of NK cell-activating receptors, such as NKG2D and NKp30, on NK cells. The ability of NK cells to produce and secrete gamma interferon (IFN-γ) also diminished after exposure to HCV-infected cells. The decline of IFN-γ production was consistent with the reduction of NK cell degranulation. In conclusion, cell-to-cell contact with HCV-infected cells negatively modulated functional capacity of NK cells, and the inhibition of NK cell function was associated with downregulation of NK-activating receptors on NK cell surfaces. These observations suggest that direct cell-to-cell interaction between NK cells and HCV-infected hepatocytes may impair NK cell function in vivo and thereby contribute to the establishment of chronic infection.
Files in This Item:
T201104706.pdf Download
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
Yonsei Authors
Park, Jeon Han(박전한) ORCID logo https://orcid.org/0000-0001-9604-3205
Yoon, Joo Chun(윤주천)
Lee, Jae Myun(이재면) ORCID logo https://orcid.org/0000-0002-5273-3113
Lim, Jong Baeck(임종백) ORCID logo https://orcid.org/0000-0003-0419-0422
사서에게 알리기


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.