Blockade of Tim-3 Pathway Ameliorates Interferon-γ Production from Hepatic CD8+ T Cells in a Mouse Model of Hepatitis B Virus Infection
Blockade of Tim-3 Pathway Ameliorates Interferon-γ Production from Hepatic CD8+ T Cells in a Mouse Model of Hepatitis B Virus Infection
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DOI：
10.1038/cmi.2009.5
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发表时间：
2009-02-01
影响因子：
24.1
通讯作者：
Ma, Chunhong
中科院分区：
文献类型：
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作者：
Ju, Ying;Hou, Nan;Ma, Chunhong
T细胞免疫球蛋白和粘蛋白结构域分子-3 （Tim-3）参与了炎症性疾病的发病机制。然而，Tim-3是否参与乙型肝炎病毒（HBV）感染尚不清楚。在此，我们研究了Tim-3在HBV感染小鼠水动力学模型中的表达和功能。从第7天到第18天，HBV模型小鼠肝T淋巴细胞，特别是CD8(+) T细胞上Tim-3的表达显著增加。通过特异性shrna敲低Tim-3后，观察到HBV模型小鼠肝CD8(+) T细胞产生的ifn - γ显著增加。非常有趣的是，我们发现Tim-3在CD8(+) T细胞上的表达在血清抗hbs产生较高的HBV模型小鼠中更高。此外，Tim-3敲低可影响体内抗hbs的产生。总的来说，我们的数据表明Tim-3可能是HBV感染中抗病毒t细胞反应的有效调节剂。细胞与分子免疫学。2009;6(1):35-43。
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. Cellular & Molecular Immunology. 2009;6(1):35-43.