Fine characterization of intrahepatic NK cells expressing natural killer receptors in chronic hepatitis B and C

Bonorino, Paula; Ramzan, Muhammad; Camous, Xavier; Dufeu‐Duchesne, Tania; Thélu, M.A.; Stürm, Nathalie; Dariz, Aurélie; Guillermet, Christiane; Pernollet, Martine; Zarski, Jean–Pierre; Marche, Patrice N.; Leroy, Vincent; Jouvin‐Marche, Evelyne

doi:10.1016/j.jhep.2009.05.030

Cited by 130 publications

(150 citation statements)

References 28 publications

(44 reference statements)

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“…This is in contrast with other studies that demonstrated that NKG2A is upregulated on NK cells during chronic HCV [18,42] and that it correlates with increased necroinflammatory score in the liver [43] and increased IL-10 production by NK cells [44]. It is possible that this is upregulation is related to the development of chronic liver disease.…”

Section: Discussioncontrasting

confidence: 87%

“…This probably reflects a shut-off mechanism to guard against liver inflammation and the development of immune suppressive IL-10 NK cells. Alternatively, it was demonstrated that HCV infected hepatocytes express enhanced levels of HLA-E and that the HLA-A2 restricted epitope HCV core AA (35)(36)(37)(38)(39)(40)(41)(42)(43)(44) stabilizes HLA-E expression [18]. Since NKG2A binds to HLA-E, enhanced expression of NKG2A by NK cells from chronic HCV patients resulted in reduced cytolysis of HLA-E expressing hepatocytes [18].…”

Section: Discussionmentioning

confidence: 99%

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

Pelletier

Drouin

Bédard

et al. 2010

Journal of Hepatology

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Background/Aims-Natural killer (NK) cells provide early defense against viral infections by killing infected cells and producing cytokines that inhibit viral replication. NK cells also interact with dendritic cells (DCs) and this reciprocal interaction regulates both innate and adaptive immunity. Genetic studies have suggested that NK cell activity is a determinant of HCV infectious outcome but a functional correlation was not established. We hypothesized that increased NK cell activity during acute HCV infection will correlate with spontaneous viral clearance.

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Section: Discussioncontrasting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

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

Pelletier

Drouin

Bédard

et al. 2010

Journal of Hepatology

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“…81 Notably, persistent HBV or HCV infection, which is the main risk factor for HCC, has been shown to influence NK cell phenotype, especially by increasing expression of inhibitory receptors and reducing expression of activating receptors (Table 3). [82][83][84][85][86][87][88][89] In one study, NK cells from chronic HCV patients had a significantly reduced expression of NKp46 and NKp30 and an increased expression of NKG2A compared with NK cells from healthy and HBV infected subjects. 88 Our group recently found a higher percentage of NKG2A 1 NK cells in peripheral blood from patients with active CHB patients than from patients with inactive CHB or from control patients.…”

Section: Downregulated Activating Receptorsmentioning

confidence: 99%

NK cell receptor imbalance and NK cell dysfunction in HBV infection and hepatocellular carcinoma

et al. 2014

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Hepatocellular carcinoma (HCC) is currently the third leading cause of cancer mortality and a common poor-prognosis malignancy due to postoperative recurrence and metastasis. There is a significant correlation between chronic hepatitis B virus (HBV) infection and hepatocarcinogenesis. As the first line of host defense against viral infections and tumors, natural killer (NK) cells express a large number of immune recognition receptors (NK receptors (NKRs)) to recognize ligands on hepatocytes, liver sinusoidal endothelial cells, stellate cells and Kupffer cells, which maintain the balance between immune response and immune tolerance of NK cells. Unfortunately, the percentage and absolute number of liver NK cells decrease significantly during the development and progression of HCC. The abnormal expression of NK cell receptors and dysfunction of liver NK cells contribute to the progression of chronic HBV infection and HCC and are significantly associated with poor prognosis for liver cancer. In this review, we focus on the role of NK cell receptors in anti-tumor immune responses in HCC, particularly HBV-related HCC. We discuss specifically how tumor cells evade attack from NK cells and how emerging understanding of NKRs may aid the development of novel treatments for HCC. Novel mono-and combination therapeutic strategies that target the NK cell receptor-ligand system may potentially lead to successful and effective immunotherapy in HCC. Keywords: activating receptor; hepatocellular carcinoma; inhibitory receptor; natural killer cell; natural killer receptor INTRODUCTION Hepatocellular carcinoma (HCC) is currently the third leading cause of cancer mortality and a common poor-prognosis malignancy due to postoperative recurrence and metastasis. 1 Common clinical risk factors for HCC include hepatitis B virus (HBV)/hepatitis C virus (HCV) infection, heavy alcohol intake, steatohepatitis and diabetes. 2 Approximately 50% of HCC cases worldwide can be attributed to chronic HBV infection (CHB) and almost 75% of HCC cases occur in developing countries where HBV is endemic. 3,4 According to statistics, older male patients who are infected with HBV genotype C or co-infected with HCV, have high levels of viral load and have been exposed to the aflatoxin, or older male patients who have a family history of HCC tend to have a high risk of developing HCC. [5][6][7] Accumulating clinical and epidemiological evidence shows a significant correlation between chronic HBV infection and hepatocarcinogenesis. However, the underlying mechanisms

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“…Although the activation of the innate immune response has a key role in initiating the adaptive immune response, experimental results of HBV infection in both chimpanzees and woodchucks demonstrated non-or limited activation of innate immunity in acute HBV infection. 5,6 A number of recent studies [7][8][9][10] have investigated and suggested the involvement of innate cells, such as nature killer and nature killer T cells, in chronic HBV infection and suggested that these cells could play a role in liver damage during reactivation. Nevertheless, the role of innate immunity in viral clearance during HBV infection is still not clear.…”

Section: Introductionmentioning

confidence: 99%

Tumor necrosis factor-alpha blockage therapy impairs hepatitis B viral clearance and enhances T-cell exhaustion in a mouse model

Chyuan

Tsai²,

Tzeng

et al. 2015

Cell Mol Immunol

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Hepatitis B virus (HBV) reactivation and recurrence are common in patients undergoing immunosuppression therapy. Tumor necrosis factor (TNF) blockage therapy is effective for the treatment of many autoimmune inflammatory diseases. However, the role of TNF-a blockage therapy in the innate and adaptive immune responses against HBV is still not clear. A detailed analysis of HBV infection under TNF-a blockage therapy is essential for the prophylaxis and therapy for HBV reactivation and recurrence. In this study, HBV clearance and T-cell responses were analyzed in a HBV-transfected mouse model under anti-TNF blockage therapy. Our results demonstrated that under TNF-a blockage therapy, HBV viral clearance was impaired with persistent elevated HBV viral load in a dose-and temporal-dependent manner. The impairment of HBV clearance under anti-TNF-a blockage therapy occurred at early time points after HBV infection. In addition, TNF-a blockade maintained a higher serum HBV viral load and increased the number of intrahepatic programmed cell death (PD)-1 high CD127 low exhausted T cells. Furthermore, TNF-a blockade abolished Toll-like receptor 9 (TLR9) ligand-induced facilitation of HBV viral clearance. Taken together, TNF-a blockade impairs HBV clearance and enhances viral load, and these effects depend on early administration after HBV infection. Our results here demonstrate that early TNF-a blockade reduces viral clearance and persistently maintains elevated HBV viral load in a mouse model, suggesting that HBV may reactivate during therapy with TNF-a-blocking agents.

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Fine characterization of intrahepatic NK cells expressing natural killer receptors in chronic hepatitis B and C

Abstract: HCV and HBV affect NK cell subsets according to the status of the diseases, especially CD3(-)CD56(dim)NKG2A(+) and CD3(-)CD56(bright)NKG2A(+) cells, may be of interest for disease monitoring.

Cited by 130 publications

References 28 publications

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

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

NK cell receptor imbalance and NK cell dysfunction in HBV infection and hepatocellular carcinoma

Tumor necrosis factor-alpha blockage therapy impairs hepatitis B viral clearance and enhances T-cell exhaustion in a mouse model

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