Clinical Significance and Functional Studies of Myeloid-Derived Suppressor Cells in Chronic Hepatitis C Patients

Cai, Weiping; Qin, Aiping; Guo, Peng; Yan, Dehong; Hu, Fengyu; Yang, Qiong; Xu, Min; Fu, Yongshui; Zhou, Jie; Tang, Xiaoping

doi:10.1007/s10875-012-9861-2

Cited by 85 publications

(113 citation statements)

References 37 publications

(58 reference statements)

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“…Accumulating evidence has demonstrated that MDSCs were closely associated with disease progression in malignancy and some inflammation-mediated pathological conditions (7,16). Although recent studies report MDSC expansion in viral infections (17)(18)(19)(20)(21)(22), phenotypic and functional features of MDSCs are still poorly defined in patients with CHB. The aim of this study was to determine whether MDSCs are involved in the impaired immune response leading to chronic HBV infection.…”

Section: Hla-drmentioning

confidence: 99%

“…For surface marker staining, fresh heparinized peripheral blood (100 ml) was labeled with the following mAbs: PE-Cy7-conjugated CD14, PE-Cy5-conjugated HLA-DR, FITC-conjugated CD11b, FITC-conjugated CD11c, PE-conjugated CD33, PE-conjugated CD80, FITC-conjugated CD86, PEconjugated PD-L1, PE-conjugated programmed death 1 (PD-1), PE-Cy7-conjugated CD11b, and FITC-conjugated Lin1 (CD3, 14,16,19,20,56) (BioLegend, San Diego, CA). After the cells were incubated for 30 min at 4˚C in the dark, they were lysed with RBC lysis solution (BioLegend).…”

Section: Flow Cytometric Analysismentioning

confidence: 99%

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Myeloid-Derived Suppressor Cells Regulate Immune Response in Patients with Chronic Hepatitis B Virus Infection through PD-1–Induced IL-10

Huang

Zhang

Yan

et al. 2014

The Journal of Immunology

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Although myeloid-derived suppressor cells (MDSCs) are well known for their immunosuppressive function in several pathological conditions, the role of MDSCs in hepatitis B virus infection remains obscure. In this study, we investigated the frequency and function of MDSCs in the peripheral blood and liver of 91 chronic hepatitis B (CHB) patients. A higher percentage of MDSCs, defined as CD14+HLA-DR−/low, was detected in peripheral blood of CHB patients than that of the healthy controls. Moreover, high expression of programmed death 1 (PD-1) and secretion of IL-10 in this population were determined. The frequency of MDSCs was positively correlated with serum viral load, but it was negatively correlated with liver inflammatory injury. These cells were also abundant in liver tissue of CHB patients and were related to necroinflammatory activity. Furthermore, we found that these cells could suppress hepatitis B virus–specific CD8+ T cell response, including reduced proliferation and IFN-γ production, and inhibit degranulation of CD8+ T cells, including reduced production of granzyme B and perforin. Importantly, PD-1–induced IL-10 production by MDSCs was responsible for the suppressive activity. To our knowledge, for the first time our study proved that CD14+HLA-DR–/lowPD-1+ MDSCs in CHB patients contribute to an inadequate immune response against the virus and lead to chronic infection, which represents a potential target for therapeutic intervention.

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Section: Hla-drmentioning

confidence: 99%

Section: Flow Cytometric Analysismentioning

confidence: 99%

Myeloid-Derived Suppressor Cells Regulate Immune Response in Patients with Chronic Hepatitis B Virus Infection through PD-1–Induced IL-10

Huang

Zhang

Yan

et al. 2014

The Journal of Immunology

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“…MDSCs suppressed T cell responses in antigen-specific and non-specific ways which was dependent on arginase-1 induction and direct cell-cell contact. Cai et al (2013) evaluated patients with chronic hepatitis C infection (CHC) pre-and postantiviral therapy (Peg-IFN-α and Ribavirin) for 48 weeks. They found a high level of MDSCs in the circulation which correlated with HCV RNA and activated CD4 + and CD8 + CD38 + T cells.…”

Section: Mdscs As a Target For Diseases Of Ageingmentioning

confidence: 99%

Ageing and myeloid-derived suppressor cells: possible involvement in immunosenescence and age-related disease

Bueno

Sant’Anna

Lord

2014

AGE

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Infections, cancer and autoimmune diseases occur more frequently in the elderly, and although many factors contribute to this, the age-related remodelling of the immune system, termed immunosenescence, plays a major role. Over the last two decades, studies have evaluated the effect of ageing on both the adaptive and innate arms of the immune system and demonstrated compromised function in several cells including lymphocytes (naïve, effector and memory), regulatory T and B cells, monocytes, neutrophils and NK cells. In addition, a well-documented feature of ageing is the increase in systemic inflammatory status (inflammageing), with raised serum levels of IL6, TNFα and CRP as well as reduced IL10. Recently, myeloid-derived suppressor cells have been the focus of many reports as these cells show immunosuppressive properties and are present in higher frequency during infections, cancer and autoimmunity. Importantly, there have been publications showing increased numbers of myeloid-derived suppressor cells in aged mice and humans. In this review, we discuss the current literature on myeloid-derived suppressor cells, their possible role in altered immune function in the elderly, and whether it may be possible to manipulate these cells to alleviate age-related immune dysfunction.

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“…In the context of virus infection, hepatitis C virus (HCV) infection could promote peripheral MDSCs accumulation and suppress T cell responses [8,9]. Also, elevated peripheral MDSCs in chronic hepatitis C patients was observed to be related to HCV-RNA copies [10].…”

Section: Introductionmentioning

confidence: 99%

Expansion of HLA-G-Expressing Myeloid-Derived Suppressor Cells in Patients with Chronic Hepatitis B Virus Infection

Lu¹,

Li²,

Lin³

et al. 2017

J Antivir Antiretrovir

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Both human leukocyte antigen-G (HLA-G) and myeloid-derived suppressor cells (MDSCs) was associated with the pathogenesis of infectious diseases. Whether peripheral MDSCs express HLA-G during virus infection remains unknown. We investigated the frequency of HLA-G + MDSCs and its subsets in patients infected with chronic hepatitis B (CHB). In this study, frequencies of peripheral MDSCs (Lin1-HLA-DR-CD33 + CD11b + ) and HLA-G expressing subsets from 50 CHB patients and 27 normal controls were analyzed using flow cytometry. Data revealed the median percentage of MDSCs was not significantly different between the CHB patients and controls (0.30% vs. 0.29%; p=0.884). Among MDSCs, similar frequency was observed for CD14+ monocytic MDSC (mMDSCs; 31.25% vs. 23.35%; p=0.063) and CD15 + granulocytic MDSC (gMDSCs; 22.60% vs. 21.55%; p=0.558) between the two groups. However, HLA-G + MDSCs was significantly increased in CHB patients compared with that of controls (3.30% vs. 0.50%; p<0.001). Furthermore, both HLA-G + mMDSCs (0.99% vs. 0.00%; p<0.001) and HLA-G + gMDSC (0.78% vs. 0.00%; p<0.001) were also dramatically increased in CHB patients. Particularly, HLA-G + gMDSC was inversely correlated to the viral DNA loads and significantly increased in HBeAb positive patients. Summary, this work reports for the first time HLA-G + MDSCs, a new population of peripheral MDSCs, were expanded in CHB patients; however, its clinical relevance yet to be further explored.

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Clinical Significance and Functional Studies of Myeloid-Derived Suppressor Cells in Chronic Hepatitis C Patients

Abstract: Our study reveals a significant correlation between MDSC levels with HCV disease progression, and their response to antiviral therapy. The arginase-1-dependent mechanism of MDSCs from CHC patients indicates that arginase-1 may be promising target for HCV immunotherapy.

Cited by 85 publications

References 37 publications

Myeloid-Derived Suppressor Cells Regulate Immune Response in Patients with Chronic Hepatitis B Virus Infection through PD-1–Induced IL-10

Myeloid-Derived Suppressor Cells Regulate Immune Response in Patients with Chronic Hepatitis B Virus Infection through PD-1–Induced IL-10

Ageing and myeloid-derived suppressor cells: possible involvement in immunosenescence and age-related disease

Expansion of HLA-G-Expressing Myeloid-Derived Suppressor Cells in Patients with Chronic Hepatitis B Virus Infection

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