https://scholars.lib.ntu.edu.tw/handle/123456789/416914
標題: | Low hepatitis B virus-specific T-cell response in males correlates with high regulatory T-cell numbers in murine models | 作者: | 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 |
公開日期: | 2017 | 出版社: | WILEY | 卷: | 66 | 期: | 1 | 起(迄)頁: | 69 | 來源出版物: | Hepatology (Baltimore, Md.) | 摘要: | 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. |
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 |
ISSN: | 0270-9139 | DOI: | 10.1002/hep.29155 | SDG/關鍵字: | 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 |
顯示於: | 微生物學科所 |
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