TITLE

HBcAg induces PD-1 upregulation on CD4+T cells through activation of JNK, ERK and PI3K/AKT pathways in chronic hepatitis-B-infected patients

AUTHOR(S)
Li, Man; Sun, Xue-Hua; Zhu, Xiao-Jun; Jin, Shu-Gen; Zeng, Zhen-Jun; Zhou, Zhen-Hua; Yu, Zhuo; Gao, Yue-Qiu
PUB. DATE
February 2012
SOURCE
Laboratory Investigation (00236837);Feb2012, Vol. 92 Issue 2, p295
SOURCE TYPE
Periodical
DOC. TYPE
Article
ABSTRACT
Hyper-expression of programmed death-1 (PD-1) is a hallmark of exhausted T cells. In chronic hepatitis-B virus (HBV)-infected patients, PD-1 upregulation on T cells was often observed. The mechanism of it has not been fully understood. In this study, we examined the dynamic changes of PD-1 expression on T cells during the natural history of chronic HBV infection and explored the signaling pathway of PD-1 upregulation by the hepatitis-B core antigen (HBcAg). Sixty-seven chronic HBV-infected patients were categorized into an immune tolerance group, an immune clearance group and an inactive virus carrier group, and 20 healthy volunteers were chosen as normal control group. Peripheral blood mononuclear cells from patients and healthy volunteers, and T lymphocytes from healthy volunteers were separated. Results showed that the PD-1 expression level on CD4+T cells in every phase of chronic HBV infection was significantly higher than that in healthy volunteers, whereas such effects were not observed on CD8+T cells. In the immune clearance phase, a positive correlation was found between serum HBV DNA level and the PD-1 expression level on CD4+T cells. In all phases, no correlation was shown between serum alanine amino transferase (ALT) level and PD-1 expression level. Phosphorylation of JNK, ERK and AKT was induced by HBcAg, and inhibitors of JNK, ERK and PI3K/AKT significantly decreased the HBcAg-induced PD-1 upregulation on CD4+T cells. In conclusion, the PD-1 expression level on CD4+T cells was upregulated in every phase of chronic HBV infection, which was induced by HBcAg through JNK, ERK and PI3K/AKT signaling pathways.
ACCESSION #
70860914

 

Related Articles

  • Predictive value of intrahepatic hepatitis B virus covalently closed circular DNA and total DNA in patients with acute hepatitis B and patients with chronic hepatitis B receiving anti-viral treatment. PENG RUAN; BOPING ZHOU; XIUFANG DAI; ZEQUN SUN; XIAOYAN GUO; JIAN HUANG; ZUOJIONG GONG // Molecular Medicine Reports;2014, Vol. 9 Issue 4, p1135 

    This study aimed to investigate the persistence and predictive values of intrahepatic (IH) hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) and total DNA (tDNA) in patients with acute hepatitis B (AHB) and patients with chronic hepatitis B (CHB) receiving anti.viral treatment. The...

  • A Randomized Trial of Peginterferon α-2a With or Without Ribavirin for HBeAg-Negative Chronic Hepatitis B. Rijckborst, Vincent; ter Borg, Martijn J.; Cakaloglu, Yilmaz; Ferenci, Peter; Tabak, Fehmi; Akdogan, Meral; Simon, Krzysztof; Raptopoulou-Gigi, Maria; Örmeci, Necati; Zondervan, Pieter E.; Verhey, Elke; van Vuuren, Anneke J.; Hansen, Bettina E.; Janssen, Harry L. A. // American Journal of Gastroenterology;Aug2010, Vol. 105 Issue 8, p1762 

    OBJECTIVES:Hepatitis B e antigen (HBeAg)-negative chronic hepatitis B patients are at high risk of treatment relapse after any antiviral therapy. Combining peginterferon α-2a with ribavirin might improve sustained response rates.METHODS:Overall, 138 HBeAg-negative chronic hepatitis B patients...

  • Expression of CD39 on FoxP3 T cells correlates with progression of HBV infection.  // BMC Immunology;2012, Vol. 13 Issue 1, p17 

    The article presents a study conducted by the authors related to association of CD39+ T cells, tregs with hepatitis B virus (HBV) infection. Analysis of HBV patients was conducted to assess association of the treg with HBV copy number and the liver injury marker alanine aminotransferase (ALT)....

  • Regulatory Role of CD4CD25Foxp3 Regulatory T Cells on IL-17-Secreting T Cells in Chronic Hepatitis B Patients. Li, Jie; Shi, Jun; Ren, Wanhua; Wu, Wei; Chen, Zhi // Digestive Diseases & Sciences;Jul2014, Vol. 59 Issue 7, p1475 

    Background: Both interleukin (IL)-17-secreting CD4 T (Th17) and CD4CD25Foxp3 T regulatory (Treg) cells have been shown to be associated with disease progression or liver damage in chronic hepatitis B (CHB) patients. However, the relationship between Treg cells and IL-17-secreting T cells in...

  • Serum HBV RNA and HBeAg are useful markers for the safe discontinuation of nucleotide analogue treatments in chronic hepatitis B patients. Tsuge, Masataka; Murakami, Eisuke; Imamura, Michio; Abe, Hiromi; Miki, Daiki; Hiraga, Nobuhiko; Takahashi, Shoichi; Ochi, Hidenori; Nelson Hayes, C.; Ginba, Hiroyuki; Matsuyama, Kazuhiro; Kawakami, Hiroiku; Chayama, Kazuaki // Journal of Gastroenterology;Oct2013, Vol. 48 Issue 10, p1188 

    Background: Treatment for chronic hepatitis B has improved drastically with the use of nucleot(s)ide analogues (NAs). However, NA therapy typically fails to eliminate Hepatitis B virus (HBV) completely, and it is difficult to discontinue these therapies. We previously demonstrated that NA...

  • e Antigen in acute hepatitis B. Norkrans, Gunnar; Magnius, Lars; Iwarson, Sten // British Medical Journal;3/27/1976, Vol. 1 Issue 6012, p740 

    Examines the association between e antigen and hepatitis-B surface antigen (HBs Ag) of patients with acute viral hepatitis B in Goteborg, Sweden. Treatment of the disease; Detection of antigen levels in the serum; Subtypes of HBs Ag; Diagnosis of hepatitis infection.

  • Adefovir dipivoxil monotherapy is a sufficiently effective treatment modality for Japanese patients with lamivudine-resistant chronic hepatitis B. Sato, Ken; Takagi, Hitoshi; Kakizaki, Satoru; Sohara, Naondo; Mori, Masatomo // Journal of Gastroenterology;Mar2006, Vol. 41 Issue 3, p283 

    The article presents a study to evaluate the efficacy of adefovir dipivoxil monotherapy for Japanese patients with lamivudine-resistant chronic hepatitis B. The study found that the alanine aminotransferase level in all the patients under observation decreased and normalized in 67 percent...

  • Entecavir versus Lamivudine for Patients with HBeAg-Negative Chronic Hepatitis B. Lai, Ching-Lung; Shouval, Daniel; Lok, Anna S.; Chang, Ting-Tsung; Cheinquer, Hugo; Goodman, Zachary; DeHertogh, Deborah; Wilber, Richard; Zink, Richard C.; Cross, Anne; Fernandes, Lori // New England Journal of Medicine;3/9/2006, Vol. 354 Issue 10, p1011 

    Background: Entecavir is a potent and selective antiviral agent that has demonstrated efficacy in phase 2 studies in patients with hepatitis B e antigen (HBeAg)–negative chronic hepatitis B. Methods: In this phase 3, double-blind trial, we randomly assigned 648 patients with...

  • Mild-to-Moderate Elevation of Alanine Aminotransferase Increases Liver Stiffness Measurement by Transient Elastography in Patients With Chronic Hepatitis B. James Fung; Ching-Lung Lai; Charles Cheng; Ringo Wu; Danny Ka-Ho Wong; Man-Fung Yuen // American Journal of Gastroenterology;Mar2011, Vol. 106 Issue 3, p492 

    OBJECTIVES:Liver stiffness measurement has been shown to be increased in severe acute flares of hepatitis. Whether lesser degree of hepatitis can also increase liver stiffness is not known. The present study aimed to investigate the effect of mild-to-moderate elevations of alanine...

Share

Read the Article

Courtesy of NEW JERSEY STATE LIBRARY

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics