Ju Ying, Hou Nan, Zhang Xiao Ning, Zhao Di, Liu Ying, Wang Jin Jin, Luan Fang, Shi Wei, Zhu Fa Liang, Sun Wen Sheng, Zhang Li Ning, Gao Cheng Jiang, Gao Li Fen, Liang Xiao Hong, Ma Chun Hong
Institute of Immunology, Shandong University School of Medicine, 44 Wenhua Xi Road, Jinan, Shandong 250012, China.
Cell Mol Immunol. 2009 Feb;6(1):35-43. doi: 10.1038/cmi.2009.5.
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.
据报道，含T细胞免疫球蛋白和粘蛋白结构域分子3（Tim-3）参与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）感染仍不清楚。在此，我们在基于流体动力学的HBV感染小鼠模型中研究了Tim-3的表达和功能。在第7天至第18天的HBV模型小鼠中，肝T淋巴细胞尤其是CD8+T细胞上Tim-3的表达显著增加。在用特异性短发夹RNA敲低Tim-3后，观察到HBV模型小鼠肝CD8+T细胞产生的干扰素-γ显著增加。非常有趣的是，我们发现血清抗-HBs产生较高的HBV模型小鼠中，CD8+T细胞上的Tim-3表达更高。此外，Tim-3敲低影响体内抗-HBs的产生。总体而言，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因子。
