Natural Killer Cells Are Polarized Toward Cytotoxicity in Chronic Hepatitis C in an Interferon-Alfa–Dependent Manner

Abstract

Background and Aims: Patients with chronic hepatitis C virus (HCV) infection display great variability in disease activity and progression. While virus-specific adaptive immune responses have been extensively characterized and found to be impaired in chronic hepatitis C, the role of innate immune responses in disease activity and progression of chronic hepatitis C is not well understood.

Natural killer p46Highexpression defines a natural killer cell subset that is potentially involved in control of hepatitis C virus replication and modulation of liver fibrosis

“…3 The exact role of NK cells in HCV infection, however, remains elusive, because current studies have yielded inconsistent results regarding phenotype and function of NK cells. [4][5][6][7][8][9][10][11][12] For example, surface expression and function of NKp46, a major activating receptor, is discussed controversially. 5,[7][8][9]33 These discrepancies might, in part, be explained by different characteristics of study cohorts and/or methodological issues.…”

“…[4][5][6][7][8][9][10][11][12] For example, surface expression and function of NKp46, a major activating receptor, is discussed controversially. 5,[7][8][9]33 These discrepancies might, in part, be explained by different characteristics of study cohorts and/or methodological issues. 28 Moreover, it is important to note that previous reports not only demonstrated varying expression of NKp46 in different NK-cell clones, but also suggested that density of NKp46 expression may correlate with cytolytic activity in vitro.…”

“…3 However, published data on phenotype and function of NK cells in HCV infection are controversial. [4][5][6][7][8][9][10][11][12][13] …”

“…3 However, published data on phenotype and function of NK cells in HCV infection are controversial. [4][5][6][7][8][9][10][11][12][13] Based on the expression of CD56, human NK cells have been divided into two functional subsets. 14 In humans, approximately 90% of circulating NK cells belong to the CD56 Dim subset, which is characterized by moderate to high expression levels of Fc-c RIIIA (CD16) and perforin, as well as high cytotoxic capability.…”

“…[17][18][19][20][21] Studies on NKp46 in HCV infection are controversial, because both reduced and increased surface expression have been reported. 5,[7][8][9] In this context, it is of interest that earlier studies showed that the surface expression of NKp46 may vary in different human peripheral blood NK cells, and that the NKp46 phenotype of NK clones correlates with cytolytic activity. 22 In the present study, we compared the ex vivo phenotypic and functional characteristics of circulating and intrahepatic NKp46 Dim and NKp46 High NK cells, and demonstrate that NKp46 surface density defines, phenotypically and functionally, different human NKcell subsets.…”