Role of T follicular helper cells and their associated molecules in the pathogenesis of chronic hepatitis B virus infection

Xing, Tongjing; Xu, Huji; Yu, Wenqing

doi:10.3892/etm.2012.864

Cited by 14 publications

(9 citation statements)

References 17 publications

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“…4 ). In contrast, the IL-21 levels secreted by Tfh cells from HBV-LC patients were significantly increased compared with those from healthy controls (5.7% ± 1.4% vs 3.4% ± 1.2%, p = 0.001), which was consistent with previous reports [ 24 , 25 ]. Another important cytokine, IFN-γ, showed a similar tendency as IL-21.…”

Section: Resultssupporting

confidence: 92%

Impaired Function of CD4+ T Follicular Helper (Tfh) Cells Associated with Hepatocellular Carcinoma Progression

Jia

Zeng

et al. 2015

PLoS ONE

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Background and AimsCD4+ T follicular helper (Tfh) cells, a new subset of immune cells, have been demonstrated to be involved in the development and prognosis of tumors. However, their functional role in human hepatocellular carcinoma (HCC) is relatively unknown, and the detailed mechanisms in HCC development remain to be described.MethodsA total of 85 HCC patients with hepatitis B virus (HBV) infection, 25 HBV-relative liver cirrhosis (LC) patients, and 20 healthy controls (HC) were randomly enrolled. Flow cytometric analysis, immunohistochemical staining, and relative function (i.e., cytokine secretion, B cell maturation) assays were used to analyze the properties of CXCR5+CD4+ T cells. In addition, the relationship between the frequency of CXCR5+CD4+ T cells and overall survival rates or disease-free survival rates was also analyzed by the Kaplan-Meier method.ResultsThe frequency of circulating CXCR5+CD4+ T cells was significantly decreased in HCC patients compared with HBV-relative liver cirrhosis (LC) patients and healthy controls, and the decrease in circulating CXCR5+CD4+ T cells correlated with disease progression. The proportion of infiltrated CXCR5+CD4+ T cells was significantly decreased in tumor regions compared with nontumor regions. Furthermore, compared with healthy controls, the function of circulating CXCR5+CD4+ T cells in HCC was impaired, with reduced IL-21 secretion and dysfunction in promoting B cell maturation. Importantly, follow-up data indicated that a decreased frequency of circulating CXCR5+CD4+ T cells was also associated with reduced disease-free survival time in HCC patients.ConclusionsImpairment of CD4+ T follicular helper cells may influence the development of HBV-associated HCC. Decreased CD4+ T follicular helper cells may represent a potential prognostic marker and serve as a novel therapeutic target for HCC patients.

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Section: Resultssupporting

confidence: 92%

Impaired Function of CD4+ T Follicular Helper (Tfh) Cells Associated with Hepatocellular Carcinoma Progression

Jia

Zeng

et al. 2015

PLoS ONE

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“…Some studies indicate that TFH cells are involved in the immune response in HBV infection and their increase in number reflects the activation of the immune response [34,35]. Studies found that the percentages of CD4 + CXCR5 + [34], CD4 + CXCR5 + ICOS + and CD4 + CXCR5 + PD-1 + [35] TFH cells were significantly higher in immune-tolerant chronic hepatitis B (CHB) patients compared to the healthy controls, consistent with our study.…”

Section: Discussionsupporting

confidence: 94%

“…Studies found that the percentages of CD4 + CXCR5 + [34], CD4 + CXCR5 + ICOS + and CD4 + CXCR5 + PD-1 + [35] TFH cells were significantly higher in immune-tolerant chronic hepatitis B (CHB) patients compared to the healthy controls, consistent with our study. Because our experimental group also belongs to immune-tolerant CHB, it is difficult to explain why the increased percentage of TFH cells is caused by HBV-MN.…”

Section: Discussionsupporting

confidence: 94%

“…However, we found that the percentage of CD4 + CXCR5 + TFH cells was significantly higher in HBV-MN patients compared to HBV-IT. Xing et al [34] found that decreased level of IL-21 in HBV-IT suggests the decrease in TFH cells activity. Our data showed that IL-21 level was significantly higher in HBV-MN patients compared to the HBV-IT and the HCs.…”

Section: Discussionmentioning

confidence: 98%

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Frequency of CD4+CXCR5+ TFH cells in patients with hepatitis b virus-associated membranous nephropathy

Liu

Zhao

et al. 2014

International Immunopharmacology

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“…However, little is known about the role of Tfh cells in the liver of mice during acute HBV infection. Several studies showed that the frequency of CD4 + CXCR5 + T cells was significantly higher in patients with chronic HBV infection than that in healthy subjects [16, 17]. In addition, a previous observation demonstrated that the frequency of intrahepatic CD4 + CXCR5 + T cells in HBV transgenic mice was significantly higher than that in wild-type mice [18].…”

Section: Discussionmentioning

confidence: 99%

Activation of intrahepatic CD4+CXCR5+ T and CD19+ B cells is associated with viral clearance in a mouse model of acute hepatitis B virus infection

Song

Lei

et al. 2016

Oncotarget

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The role of immunity in the pathogenesis of acute hepatitis B virus (HBV) infection is poorly understood. The purpose of this research was to define the intrahepatic immune factors responsible for viral clearance during acute HBV infection. The model of acute HBV infection was established by hydrodynamically transfecting mice with pCDNA3.1-HBV1.3 plasmids which contained a supergenomic HBV1.3-length transgene. The frequency of CD4+ CXCR5+ T cells, CD19+ B cells and their surface molecules in livers, spleens and peripheral blood were detected using flow cytometry. The lymphomononuclear cells isolated from the livers of transfected mice were further stimulated by HBc-derived peptides and then the frequency and cytokine secretion of HBV-specific CD4+CXCR5+ T cells were detected. We found that the frequency of CXCR5+ in CD4+ T cells was specifically increased; the expression of PD-1 was decreased while the expression of ICOS was increased on intrahepatic CD4+CXCR5+ T cells. Although the frequency of CD19+ B cells was not affected, the expression of PDL-1, ICOSL and IL-21R on B cells was increased in the livers of mice. The frequency of HBV-specific CD4+CXCR5+ T cells and the production of IL-21 by intrahepatic CD4+CXCR5+ T cells of mice with acute HBV infection were increased after stimulation. Furthermore, the expression of function-related molecules of intrahepatic CD4+CXCR5+ T, including Bcl-6, CXCR5, IL-6, IL-6R, IL-21 and IL-4 in the liver was increased during acute HBV infection. In conclusion, the activation of intrahepatic CD4+CXCR5+ T cells and B cells was associated with the clearance of HBV during acute infection.

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Role of T follicular helper cells and their associated molecules in the pathogenesis of chronic hepatitis B virus infection

Cited by 14 publications

References 17 publications

Impaired Function of CD4+ T Follicular Helper (Tfh) Cells Associated with Hepatocellular Carcinoma Progression

Impaired Function of CD4+ T Follicular Helper (Tfh) Cells Associated with Hepatocellular Carcinoma Progression

Frequency of CD4+CXCR5+ TFH cells in patients with hepatitis b virus-associated membranous nephropathy

Activation of intrahepatic CD4+CXCR5+ T and CD19+ B cells is associated with viral clearance in a mouse model of acute hepatitis B virus infection

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