Blockade of Tim-3 pathway ameliorates interferon-gamma production from hepatic CD8+ T cells in a mouse model of hepatitis B virus infection.
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.
Ju
Ying
Y
Institute of Immunology, Shandong University School of Medicine, 44 Wenhua Xi Road, Jinan, Shandong 250012, China.
Hou
Nan
N
Zhang
Xiao Ning
XN
Zhao
Di
D
Liu
Ying
Y
Wang
Jin Jin
JJ
Luan
Fang
F
Shi
Wei
W
Zhu
Fa Liang
FL
Sun
Wen Sheng
WS
Zhang
Li Ning
LN
Gao
Cheng Jiang
CJ
Gao
Li Fen
LF
Liang
Xiao Hong
XH
Ma
Chun Hong
CH
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*
C442241:Havcr2 protein, mouse; D000072597:Hepatitis A Virus Cellular Receptor 2; D011991:Receptors, Virus; D007371:Interferon-gamma