Impairment of natural killer (NK) cytotoxic activity in hepatitis C virus (HCV) infection

Abstract

SUMMARYIn the present study, we evaluated the NK cell cytotoxic activity in a group of HCV-infected individuals. Although the number of NK cells present in the peripheral blood of the HCV-infected patients was comparable to non-infected individuals, spontaneous NK cytotoxicity was four-fold lower (P < 0 . 001) than in normal donors. This functional impairment was not overcome by depletion of adherent or B cells, and it was partially restored by short-term (18 h) stimulation with IL-2. However, long-term stimulation (72 h) with this lymphokine induced activated killer cell (LAK) activity comparable to normal controls. The reduction in NK cytotoxic response does not seem to be due to soluble suppressive factors, since incubation of normal peripheral blood mononuclear cells (PBMC) with infectious HCV serums for a 4-h period does not affect NK spontaneous cytotoxic activity. Successful in vitro infection of PBMC with HCV infectious serum also resulted in an impairment of NK cytotoxicity, suggesting that altered NK function is associated with HCV infection and may be responsible, at least in part, for the chronicity of the infection.

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.…”

“…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.…”

Decreased NK cell frequency in chronic hepatitis C does not affectex vivo cytolytic killing

“…11 Two subsequent studies used NK cells from healthy subjects treated in vitro with anti-CD16, HCV E2, and anti-E2 to recapitulate NK cell activation by HCV, and found diminished NK cell function in those situations. 9,10 A third study suggested that dendritic cells from HCVinfected individuals were impaired and unable to activate NK cells for maximal function.…”

“…However, studies of ex vivo NK cell function in patients with chronic hepatitis C have yielded mixed results. Corado and colleagues first reported that NK cell cytotoxicity was compromised in chronic hepatitis C compared with healthy negative controls, 11 using a well-established human NK cell target cell line, K562. 12 Similar data were published by Par and colleagues, 13 but Duesberg et al recently demonstrated that cytotoxicity and antibody-dependent cell-mediated cytotoxicity against HT29 cells were not adversely affected in chronic hepatitis C. 14 Moreover, Kawarabayashi et al found no difference in K562 cytolysis between liver mononuclear cells containing a mean of 31% CD56 ϩ NK cells between 12 HCV-negative and 12 HCV-infected subjects without cirrhosis.…”