Decreased Peripheral Natural Killer Cells Activity in the Immune Activated Stage of Chronic Hepatitis B

Li, Yuan; Wang, Jiu-Jun; Gao, Shan; Liu, Qian; Bai, Jia; Zhao, Xueqi; Hao, Yixue; Ding, Haiyan; Zhu, Fan; Yang, Dongliang; Zhao, Xingwei

doi:10.1371/journal.pone.0086927

Cited by 43 publications

(42 citation statements)

References 41 publications

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“…Indeed, accumulating evidence has indicated the critical roles of NK cells in HBV-related diseases. The number and activity of circulating NKs are remarkably decreased in patients with CHB [58][59][60] , and impaired NK function leads to persistent HBV infection and HCC tumorigenesis [61] . Tim-3 also appears to have conflicting effects on NKs.…”

Section: Tim-3 and Nk/nktsmentioning

confidence: 99%

Role of Tim-3 in hepatitis B virus infection: An overview

Liu

Gao

Liang

et al. 2016

WJG

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Hepatitis B virus (HBV) infection has received increasing public attention. hBV is the prototypical member of hepadnaviruses, which naturally infect only humans and great apes and induce the acute and persistent chronic infection of hepatocytes. A large body of evidence has demonstrated that dysfunction of the host anti-viral immune response is responsible for persistent HBV replication, unresolved inflammation and disease progression. Many regulatory factors are involved in immune dysfunction. Among these, T cell immunoglobulin domain and mucin domain-3 (Tim-3), one of the immune checkpoint proteins, has attracted increasing attention due to its critical role in regulating both adaptive and innate immune cells. In chronic HBV infection, Tim-3 expression is elevated in many types of immune cells, such as T helper cells, cytotoxic T lymphocytes, dendritic cells, macrophages and natural killer cells. Tim-3 over-expression is often accompanied by impaired function of the abovementioned immunocytes, and Tim-3 inhibition can at least partially rescue impaired immune function and thus promote viral clearance. A better understanding of the regulatory role of Tim-3 in host immunity during HBV infection will shed new light on the mechanisms of hBV-related liver disease and suggest new therapeutic methods for intervention.

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Section: Tim-3 and Nk/nktsmentioning

confidence: 99%

Role of Tim-3 in hepatitis B virus infection: An overview

Liu

Gao

Liang

et al. 2016

WJG

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“…Signifi cant reduction in the number of NK cells was observed in chronic HBV patients compared with healthy controls. 18,19 The absence of changes in total NK cells [CD3-(CD16+56)+] in our study could be due to the fact that these cells are involved in the early, nonspecifi c immune response against the virus. 20 found an increased proportion, but not absolute number of activated CD8+CD38+ T cells in patients with chronic hepatitis B in comparison with HBV carriers and healthy controls, and the percentage decreases to normal values as a result of NA therapy.…”

Section: Discussionmentioning

confidence: 79%

Immune Cell Subsets Evaluation as a Predictive Tool for Hepatitis B Infection Outcome and Treatment Responsiveness

et al. 2017

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Background: The patient's immune response is one of the major factors infl uencing HBV eradication or chronifi cation, and it is thought to be responsible for the treatment success. Aim: Our study aimed to investigate whether cellular defense mechanisms are associated with the course of HBV infection (spontaneous recovery [SR] or chronifi cation [CHB]) and with the therapeutic approach. Patients and methods: A total of 139 patients (118 with CHB, 21 SR) and 29 healthy individuals (HI) were immunophenotyped by fl owcytometry. Fifty-six patients were treatment-naïve, 20 were treated with interferons and 42 with nucleoside/nucleotide analogues. Results: Defi ciency of T lymphocytes, helper-inducer (CD3+CD4+), suppressorcytotoxic (CD8+CD3+) and cytotoxic (CD8+CD11b-, CD8+CD28+) subsets, activated T cells (CD3+HLA-DR+, CD8+CD38+) and increased CD57+CD8-cells, elevated percentages of B lymphocytes and NKT cells were observed in CHB patients compared with HI. In SR patients, elevated CD8+CD11b+, NKT and activated T cells were found in comparison with controls. The higher values of T cells and their subsets in SR patients than in CHB patients refl ect a recovery of cellular immunity in resolved HBV infection individuals. In both groups of treated patients, reduced T lymphocytes, CD3+CD4+ and CD8+CD38+ subsets were found in comparison with HI. Higher proportions of cytotoxic subsets were observed in treated patients compared with treatment-naïve CHB patients, more pronounced in the group with interferon therapy. Conclusion: Our data demonstrate that cellular immune profi les may be of prognostic value in predicting the clinical course of HBV infection, and the determination of the therapeutic response.

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“…On the other hand, the differences between the groups reported in this study are remarkable and highly statistically significant, strengthening the importance of this exploratory analysis. It is worth noting that the inflammatory infiltrate in the liver infected by HBV is particularly rich in NK cells (30–40% of total intrahepatic lymphocytes), and NK activity is high early in HBV infection and during the incubation time, suggesting that these cells are important in the pathogenesis of CHB . Although the ability of NK cells to contribute to control of HBV has been demonstrated in mouse models, their importance in human HBV‐infected liver is still unclear (innocent bystanders or potent players?)…”

Section: Discussionmentioning

confidence: 99%

KIR2DL3 and the KIR ligand groups HLA‐A‐Bw4 and HLA‐C2 predict the outcome of hepatitis B virus infection

Bona

Aiello

Colomba

et al. 2017

Journal of Viral Hepatitis

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Summary Killer immunoglobulin‐like receptors (KIRs) regulate the activation of natural killer cells through their interaction with human leucocyte antigens (HLA). KIR and HLA loci are highly polymorphic, and certain HLA‐KIR combinations have been found to protect against viral infections. In this study, we analysed whether the KIR/HLA repertoire may influence the course of hepatitis B virus (HBV) infection. Fifty‐seven subjects with chronic hepatitis B (CHB), 44 subjects with resolved HBV infection and 60 healthy uninfected controls (HC) were genotyped for KIR and their HLA ligands. The frequency of the HLA‐A‐Bw4 ligand group was higher in CHB (58%) than subjects with resolved infection (23%) (crude OR, 4.67; P<.001) and HC (10%) (crude OR, 12.38; P<.001). Similar results were obtained for the HLA‐C2 ligand group, more frequent in CHB (84%), than subjects with resolved infection (70%) (crude OR, 2.24; P<.10) and HC (60%) (crude OR, 3.56; P<.01). Conversely, the frequency of KIR2DL3 was lower in CHB (81%) than in subjects with resolved infection (98%) (crude OR, 0.10; P<.05). These results suggest a detrimental role of HLA‐A‐Bw4 and HLA‐C2 groups, which are associated with the development of CHB, and a protective role of KIR2DL3. A stepwise variable selection procedure, based on multiple logistic regression analysis, identified these three predictive variables as the most relevant, featuring high specificity (90.9%) and positive predictive value (87.5%) for the development of CHB. Our results suggest that a combination of KIR/HLA gene/alleles is able to predict the outcome of HBV infection.

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Decreased Peripheral Natural Killer Cells Activity in the Immune Activated Stage of Chronic Hepatitis B

Cited by 43 publications

References 41 publications

Role of Tim-3 in hepatitis B virus infection: An overview

Role of Tim-3 in hepatitis B virus infection: An overview

Immune Cell Subsets Evaluation as a Predictive Tool for Hepatitis B Infection Outcome and Treatment Responsiveness

KIR2DL3 and the KIR ligand groups HLA‐A‐Bw4 and HLA‐C2 predict the outcome of hepatitis B virus infection

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