title: Blockade of Tim-3 pathway ameliorates interferon-gamma production from hepatic CD8+ T cells in a mouse model of hepatitis B virus infection.
abstract: T cell immunoglobulin- and mucin-domain-containing molecule-3 (Tim-3) has been reported to participate in the pathogenesis of inflammatory diseases. However, whether Tim-3 is involved in hepatitis B virus (HBV) infection remains unknown. Here, we studied the expression and function of Tim-3 in a hydrodynamics-based mouse model of HBV infection. A significant increase of Tim-3 expression on hepatic T lymphocytes, especially on CD8+ T cells, was demonstrated in HBV model mice from day 7 to day 18. After Tim-3 knockdown by specific shRNAs, significantly increased IFN-gamma production from hepatic CD8+ T cells in HBV model mice was observed. Very interestingly, we found Tim-3 expression on CD8+ T cells was higher in HBV model mice with higher serum anti-HBs production. Moreover, Tim-3 knockdown influenced anti-HBs production in vivo. Collectively, our data suggested that Tim-3 might act as a potent regulator of antiviral T-cell responses in HBV infection.
authors.affiliation: Institute of Immunology, Shandong University School of Medicine, 44 Wenhua Xi Road, Jinan, Shandong 250012, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ju
authors.forename: Nan
authors.initials: N
authors.lastname: Hou
authors.forename: Xiao Ning
authors.initials: XN
authors.lastname: Zhang
authors.forename: Di
authors.initials: D
authors.lastname: Zhao
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Jin Jin
authors.initials: JJ
authors.lastname: Wang
authors.forename: Fang
authors.initials: F
authors.lastname: Luan
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.forename: Fa Liang
authors.initials: FL
authors.lastname: Zhu
authors.forename: Wen Sheng
authors.initials: WS
authors.lastname: Sun
authors.forename: Li Ning
authors.initials: LN
authors.lastname: Zhang
authors.forename: Cheng Jiang
authors.initials: CJ
authors.lastname: Gao
authors.forename: Li Fen
authors.initials: LF
authors.lastname: Gao
authors.forename: Xiao Hong
authors.initials: XH
authors.lastname: Liang
authors.forename: Chun Hong
authors.initials: CH
authors.lastname: Ma
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D004195:Disease Models, Animal; D055785:Gene Knockdown Techniques; D000072597:Hepatitis A Virus Cellular Receptor 2; D006509:Hepatitis B / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000276:immunology; D008099:Liver / Q000276:immunology* / Q000473:pathology / Q000821:virology; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*
chemical_list: C442241:Havcr2 protein, mouse; D000072597:Hepatitis A Virus Cellular Receptor 2; D011991:Receptors, Virus; D007371:Interferon-gamma