Increased degranulation of natural killer cells during acute HCV correlates with the magnitude of virus-specific T cell responses

Pelletier, Sandy; Drouin, Christian A.; Bédard, Nathalie; Khakoo, Salim I.; Bruneau, Julie; Shoukry, Naglaa H.

doi:10.1016/j.jhep.2010.05.013

Cited by 105 publications

(108 citation statements)

References 48 publications

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“…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.…”

Section: Discussionmentioning

confidence: 99%

“…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] …”

mentioning

confidence: 99%

“…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.…”

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confidence: 99%

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Natural killer p46High expression defines a natural killer cell subset that is potentially involved in control of hepatitis C virus replication and modulation of liver fibrosis

et al. 2012

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Natural killer (NK) cells play a role in the early control and natural course of hepatitis C virus (HCV) infection. NK cell function is regulated by a multitude of receptors, including activating NKp46 receptor. However, reports on NKp46 in hepatitis C are controversial. Therefore, we investigated the hepatic recruitment and function of NKp46(1) NK cells, considering differential surface expression of NKp46 resulting in NKp46 High and NKp46 Dim subsets. Intra-and extrahepatic NK-cell subsets from HCV-infected patients were characterized by flow cytometry. Cytotoxic activity and interferon-gamma (IFN-c) secretion were studied using K-562, P815, and primary hepatic stellate cells as targets. Anti-HCV activity of NK-cell subsets was studied using the replicon system. Density of NKp46 surface expression clearly segregated NKp46 Dim and NKp46 High subsets, which differed significantly with respect to the coexpression of maturation markers and NK-cell receptors. More important, NKp46 High NK cells showed a higher cytolytic activity and stronger IFN-c secretion than NKp46 Dim NK cells. Accordingly, NKp46 High NK cells efficiently blocked HCV replication in vitro. Blocking experiments confirmed an important role for the NKp46 receptor. Furthermore, we found an intrahepatic accumulation of NKp46 High NK cells. Of note, high cytolytic activity of NKp46 High NK cells was also confirmed in the intrahepatic NK-cell population, and the frequency of intrahepatic NKp46 High NK cells was inversely correlated with HCV-RNA levels and fibrosis stage. Conclusions: NKp46 High expression defines a specific NK-cell subset that may be involved in both the suppression of HCV replication and HCV-associated liver damage underpinning the role of NK cells in the immunopathogenesis of HCV. (HEPATOLOGY 2012;56:1201-1213 See Editorial on Page 1197 I nfection with the hepatitis C virus (HCV) often results in chronic liver disease. Elimination of HCV infection requires the coordinated function of the innate and the adaptive immune system. Natural killer (NK) cells constitute a major component of the intrahepatic lymphocyte pool. In contrast to the peripheral blood, which contains approximately 5%-10% NK cells, intrahepatic lymphocytes comprise approximately 30% NK cells, and the percentage of intrahepatic NK cells may increase >50% in liver diseases. 1 Immunogenetic analyses indicate that NK cells may influence the outcome of acute HCV infection as well as immunopathogenesis in chronic hepatitis C (CHC). 2 Accordingly, in vitro studies suggest that NK cells are able to recognize and kill HCV-infected hepatocytes in vivo. 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]

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Section: Discussionmentioning

confidence: 99%

“…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] …”

mentioning

confidence: 99%

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confidence: 99%

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Natural killer p46High expression defines a natural killer cell subset that is potentially involved in control of hepatitis C virus replication and modulation of liver fibrosis

et al. 2012

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“…Additionally, Elletier et al, (2010) In line with this, a Japanese study demonstrated that combination therapy of pegylated interferon (IFN-α) and ribavirin improved NK distribution and functions, and significantly increased their numbers among HCV -cleared patients. The authors observed that relapsing patients failed to recover NK functions and numbers, these results suggest that NK alteration caused by HCV infection may be due to the impairment of cellular immune response, which might result in chronic diseases.…”

Section: Resultsmentioning

confidence: 77%

Flow Cytometric Detection of Natural Killer Cells and Natural Killer T Cells Changes in the Blood of Patients with Chronic Hepatitis C Virus Infection in an Egyptian University Hospital

Shalaby¹,

Eshra²,

Sharaby³

et al. 2017

Int.J.Curr.Microbiol.App.Sci

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“…Werner et al describe a strong NK cell response in healthcare workers with low-level HCV exposure but do not develop into acute HCV infection [30]. Notably, Pelletier et al find an increased NK cell degranulation in early phase of HCV infection in a cohort of intravenous (IV) drug users who cleared HCV spontaneously [31]. Peter et al [32] also suggest that sustained NK cell activation protected highly-exposed uninfected injecting drug users from HCV infection.…”

Section: Nk Cells and Hcv Infectionmentioning

confidence: 99%

Natural Killer Cells in HCV Infection

Lü¹,

Shen²

2017

J Clin Cell Immunol

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Natural killer (NK) cells play a vital role in controlling viral infection. This commentary will introduce the alteration of NK cells in different infected status involving frequencies, phenotypes and functions. Moreover, it highlights the function of antibody-dependent cell-mediated cytotoxicity (ADCC) in HCV and other virus infection, and concerns its role in vaccine development and immunotherapies.

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Increased degranulation of natural killer cells during acute HCV correlates with the magnitude of virus-specific T cell responses

Cited by 105 publications

References 48 publications

Natural killer p46High expression defines a natural killer cell subset that is potentially involved in control of hepatitis C virus replication and modulation of liver fibrosis

Natural killer p46High expression defines a natural killer cell subset that is potentially involved in control of hepatitis C virus replication and modulation of liver fibrosis

Flow Cytometric Detection of Natural Killer Cells and Natural Killer T Cells Changes in the Blood of Patients with Chronic Hepatitis C Virus Infection in an Egyptian University Hospital

Natural Killer Cells in HCV Infection

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