NK细胞影响T细胞向腺病毒感染的小鼠肝脏聚集的研究

The role of NK cells in T cell recruitment into the adenovirus infected liver

目的 使用腺病毒感染的小鼠模型研究NK细胞向肝脏聚集过程中的作用机制。方法 应用抗NK1.1+ 单克隆抗体来剔除小鼠体内的NK细胞 ,使用FACS分析腺病毒感染的小鼠模型中肝脏的浸润淋巴细胞 ,应用RT PCR检测小鼠肝组织、肝浸润淋巴细胞和脾组织中的趋化因子及其受体的基因表达 ,同时测定血清ALT来估价肝损伤。结果 抗NK1.1+ 单克隆抗体明显干扰了腺病毒感染小鼠模型中的T细胞向肝脏的聚集 ,抑制了趋化因子IP 10mRNA的表达。同时 ,与未给予抗NK1.1+ 单克隆抗体的小鼠腺病毒感染模型相比较 ,其肝脏受损也明显减轻。IP 10的特异性受体CXCR3mRNA的表达先后分别出现在腺病毒感染后的脾脏和肝脏浸润淋巴细胞中。结论 NK细胞在T细胞向腺病毒感染的肝脏聚集过程中起着关键的作用 ,这种作用可能与依赖NK细胞的趋化因子IP

Objective To study the role of NK cells in T cell recruitment into murine liver infected with virus. Methods Mice were injected i.p daily with anti-NK1.1 + antibody to deplete NK cells. Lymphocytes in the liver tissue of mice infected with type 5 adenovirus depleted in the E1 and E3 regions, assessed by FACS. Expression of chemokine IP-10 and its receptor CXCR3 mRNA in the liver, hepatic lymphocytes and spleen tissue was examined by reverse transcriptional polymerase chain reaction (RT-PCR). Serum ALT was measured as indicator of liver injury. Results Anti-NK1.1 + monoclonal antibody, which was intraperitoneally injected into the mice infected with adenovirus, inhibited T cell recruitment to the liver and expression of IP-10 of lymphocytes in the liver. Slight liver injury was also observed. In the mouse model, expression of CXCR3 mRNA in spleen and liver tissue was observed at different time. Conclusion NK cells play a key role in T cell recruitment into the liver of mouse infected with adenovirus. This kind of role initiated by NK cell dependent chemokine IP-10, which induces the activated T cells priming in the spleen to the liver of the mouse, then T cells and NK cells lysis hepatocytes infected with adenovirus and result in liver injury.