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  4. Low hepatitis B virus-specific T-cell response in males correlates with high regulatory T-cell numbers in murine models
 
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Low hepatitis B virus-specific T-cell response in males correlates with high regulatory T-cell numbers in murine models

Journal
Hepatology (Baltimore, Md.)
Journal Volume
66
Journal Issue
1
Pages
69
Date Issued
2017
Author(s)
Kosinska, Anna D
Pishraft-Sabet, Leila
Wu, Weimin
Fang, Zhong
Lenart, Marzena
Chen, Jieliang
Dietze, Kirsten K
Wang, Cong
Kemper, Thekla
YONG-JUN LIN
SHIOU-HWEI YEH  
Liu, Jia
Dittmer, Ulf
Yuan, Zhenghong
Roggendorf, Michael
Lu, Mengji
DOI
10.1002/hep.29155
URI
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85019760170&doi=10.1002%2fhep.29155&partnerID=40&md5=90692123daceb83aeec801a2b8e886bd
https://scholars.lib.ntu.edu.tw/handle/123456789/416914
URL
https://api.elsevier.com/content/abstract/scopus_id/85019760170
Abstract
Hepatitis B virus (HBV) infection shows significant gender-related differences in pathogenesis, disease progression, and development of hepatocellular carcinoma. The gender-associated differences in HBV replication and viral protein levels may be associated with distinct HBV-specific immune responses in the host. In the present study, we examined the impact of gender on HBV-specific immune responses in two different mouse models representing transient and persistent hepadnaviral infection; hydrodynamic injection with the HBV genome mimicked acute HBV infection, whereas the efficacy of therapeutic vaccination was studied in the woodchuck hepatitis virus transgenic mouse model. Consistent with previous reports, significantly higher HBV DNA and protein levels were detected in male compared to female mice. Although hydrodynamic injection with the HBV genome resulted in similar numbers of intrahepatic HBV-specific cluster of differentiation 8-positive (CD8+ ) T cells, their functionality was significantly reduced in males and correlated with higher numbers of intrahepatic regulatory T cells (Tregs). Similar effects were observed in woodchuck hepatitis virus transgenic mice immunized with a DNA prime-recombinant adenovirus boost vaccination protocol. Male mice showed functionally suppressed woodchuck hepatitis virus-specific CD8+ T-cell responses in the liver and significantly higher numbers of intrahepatic Tregs compared to females. Blockade of Treg responses in male mice led to augmented effector functions of specific CD8+ T cells and subsequently improved virus control in both models of transient and persistent hepadnaviral infection.
SDGs

[SDGs]SDG3

Other Subjects
DNA vaccine; viral protein; virus DNA; hepatitis B vaccine; Adenoviridae; animal cell; animal experiment; animal model; Article; CD8+ T lymphocyte; cellular immunity; controlled study; DNA immunization; female; gene expression; hepadnavirus infection; hepatitis B; Hepatitis B virus; hydrodynamics; injection; lymphocyte count; lymphocyte function; male; mouse; murine model; nonhuman; persistent virus infection; priority journal; regulatory T lymphocyte; transgenic animal; virus genome; virus immunity; virus recombinant; virus replication; virus strain; Woodchuck hepatitis virus; analysis of variance; animal; C57BL mouse; cell culture; cellular immunity; comparative study; disease model; hepatitis B; Hepatitis B virus; immunology; lymphocyte count; nonparametric test; physiology; procedures; randomization; regulatory T lymphocyte; risk factor; sex difference; transgenic mouse; vaccination; Analysis of Variance; Animals; Cells, Cultured; Disease Models, Animal; Female; Hepatitis B; Hepatitis B Vaccines; Hepatitis B virus; Immunity, Cellular; Lymphocyte Count; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Random Allocation; Risk Factors; Sex Factors; Statistics, Nonparametric; T-Lymphocytes, Regulatory; Vaccination
Publisher
WILEY
Type
journal article

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