Decrease in CD3-negative-CD8dim+ and Vδ2/Vγ9 TcR+ peripheral blood lymphocyte counts, low perforin expression and the impairment of natural killer cell activity is associated with chronic hepatitis C virus infection

Pár, Gabriella; Rukavina, Daniel; Podack, Eckhard R.; Horányi, Margit; Szekeres-Barthó, Júlia; Hegedűs, Géza; Paál, M; Szereday, László; Mózsik, Gyula; Pár, Alajos

doi:10.1016/s0168-8278(02)00218-0

Cited by 85 publications

(28 citation statements)

References 42 publications

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“…A study by Morishima et al [17] demonstrated a decline of circulating NK cells in patients with chronic HCV infection by approximately 30%, which was corroborated by a subsequent study performed by Golden-Mason et al [19] involving a homogeneous cohort of HCV-exposed individuals from a single source in that the relative proportion of NK cells was significantly reduced in chronic HCV-infected individuals compared with resolvers and healthy controls. Similar results were obtained by previous investigations [34,35], whilst other groups indicated that peripheral NK cell counts were unchanged in hepatitis C [36,37,38]. The reasons for these conflicting results are currently unclear.…”

Section: Discussionsupporting

confidence: 82%

Frequency and Phenotype of Human Circulating and Intrahepatic Natural Killer Cell Subsets Is Differentially Regulated according to Stage of Chronic Liver Disease

Zimmermann

Mueller²,

Seidler³

et al. 2013

Digestion

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Background/Aims: Experimental liver injury models have indicated that natural killer (NK) cells are critical regulators of inflammation and fibrosis. However, data on NK cells and subsets in patients with liver diseases are limited. We thus comprehensively characterized peripheral and hepatic NK cell subsets in patients with chronic liver diseases (CLDs) of different etiologies and fibrosis stages. Methods: NK cells and other lymphocyte populations were characterized by FACS in 189 CLD patients (71 non-cirrhosis, 118 cirrhosis) and 153 healthy controls in blood and liver biopsies (n = 40). Results: In contrast to other lymphocyte subsets, circulating NK cells were generally reduced in CLD patients. Patients with fibrosis displayed a distinct increase of CD16^- NK cells in blood and of the CD16⁺ NK cell subset in liver. Patients with cirrhosis had overall lymphopenia, including reduced peripheral NK cells. Most pronounced shifts in NK cell subsets in blood and liver were found in cholestatic and autoimmune CLDs. Blood NK cells and subsets correlated with liver function, and inversely with fibrosis markers and inflammatory cytokines. Conclusions: The close association of humanNK cells with disease severity and the intrahepatic accumulation of CD16⁺ NK cells in early fibrosis favor the concept of beneficial NK cell functions in hepatofibrogenesis.

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Section: Discussionsupporting

confidence: 82%

Frequency and Phenotype of Human Circulating and Intrahepatic Natural Killer Cell Subsets Is Differentially Regulated according to Stage of Chronic Liver Disease

Zimmermann

Mueller²,

Seidler³

et al. 2013

Digestion

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show abstract

“…A number of clinical observations support the antifibrogenic effects of NK cells in patients with chronic liver disease. Although there is no consensus on whether NK cell activity is decreased in HCV-infected patients [59][60][61], an inverse correlation between NK activity and liver fibrosis grade has been reported in patients with chronic HCV infection, suggesting that NK cells may negatively regulate liver fibrosis [61]. Moreover, treatment with IFN-α, a potent activator of NK cells, has been shown to ameliorate liver fibrosis in HCV patients who responded to RAE-1 NKG2D iKIR IFN-α therapy, as well as in some patients failing to clear the virus in response to this regimen [62,63].…”

Section: Clinical Evidence For a Role Of Nk Cells In Inhibiting Livermentioning

confidence: 99%

Activation of natural killer cells inhibits liver fibrosis: a novel strategy to treat liver fibrosis

Gao

Radaeva

Jeong

2007

Expert Review of Gastroenterology & Hepatology

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Liver lymphocytes are enriched in natural killer (NK) cells, which are involved in innate immune defenses against viral infection and tumor transformation in the liver. Recent evidence indicates that NK cell activation by IFN-alpha, IFN-gamma or dsRNA attenuates liver fibrosis through the direct killing of activated hepatic stellate cells (HSCs). Interestingly, NK cells do not kill quiescent or fully activated HSCs, but only early-activated HSCs, as only these cells express elevated levels of the NK cell-activating ligand retinoic acid-induced early transcript (RAE)-1 and TNF-related apoptosis-inducing ligand receptors, in addition to downregulated levels of the NK-cell inhibitory ligand, MHC-I. Inhibition of liver fibrosis by NK cells can also be achieved through production of IFN-gamma, which induces HSC cell cycle arrest and apoptosis in a STAT1-dependent manner. Clinically, it has also been observed that NK cell activity is negatively correlated with liver fibrosis in patients with chronic hepatitis C infection. Therefore, since NK cells inhibit liver fibrosis, stimulating NK activity could potentially be a novel strategy to treat liver fibrosis. Clinical studies will be required to confirm whether stimulating NK cell activity is effective and safe in treating human liver fibrosis.

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“…The importance of innate immune cells is further emphasized by the observation that natural killer (NK) and natural T (NT) cells are uniquely enriched in the inflammatory cell infiltrate of the diseased liver [5,6]. Moreover, NK cell frequencies have been reported to be reduced in patients with chronic HCV infection [7][8][9][10], but whether this translates into altered function is still controversial [10][11][12]. To assess whether variations in the frequency and phenotype of NK and NT cells were associated with clinical, biochemical and virological indicators of disease severity and progression, we prospectively examined these cells in patients with recurrent hepatitis C post-OLT and controls.…”

Section: Introductionmentioning

confidence: 99%

Prospective study of natural killer cell phenotype in recurrent hepatitis C virus infection following liver transplantation

Varchetta

Oliviero

Donato³

et al. 2009

Journal of Hepatology

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Decrease in CD3-negative-CD8dim+ and Vδ2/Vγ9 TcR+ peripheral blood lymphocyte counts, low perforin expression and the impairment of natural killer cell activity is associated with chronic hepatitis C virus infection

Cited by 85 publications

References 42 publications

Frequency and Phenotype of Human Circulating and Intrahepatic Natural Killer Cell Subsets Is Differentially Regulated according to Stage of Chronic Liver Disease

Frequency and Phenotype of Human Circulating and Intrahepatic Natural Killer Cell Subsets Is Differentially Regulated according to Stage of Chronic Liver Disease

Activation of natural killer cells inhibits liver fibrosis: a novel strategy to treat liver fibrosis

Prospective study of natural killer cell phenotype in recurrent hepatitis C virus infection following liver transplantation

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