调节性T细胞在3型鼠肝炎病毒诱导的小鼠暴发型肝炎模型中作用的初步探讨

Primary study of regulatory T cells in murine hepatitis virus type 3 induced murine fulminant viral hepatitis

目的检测调节性T细胞（Tr）在3型鼠肝炎病毒（MHV-3）诱导的小鼠暴发型肝炎模型中的比例变化及细胞因子表达，初步探讨Tr在该疾病模型中的作用。方法通过腹腔注射MHV-3感染BALB／cJ小鼠诱导暴发型肝炎，观察小鼠的生存时间，检测血清谷丙转氨酶（ALT）、谷草转氨酶（AST）水平，利用苏木精-伊红（HE）染色法检测肝脏病理学改变，分离感染不同时间点外周血、脾脏以及肝脏中的淋巴细胞，利用流式细胞术来检测Tr的比例以及细胞因子IL-10表达水平。结果BALB／cJ小鼠感染MHV-3后，全部在3—6d内死亡，血清ALT、AST水平随着感染时间延长逐渐升高，HE染色显示肝脏组织炎症及坏死程度逐渐加重，流式细胞术检测发现随着感染时间延长，小鼠肝脏中的rrr的比例明显升高。同时肝脏Tr分泌细胞因子IL-10的比例以及肝脏组织IL-10的mRNA水平逐渐升高。结论MHV-3诱导的小鼠暴发型肝炎模型中Tr在肝脏中的比例和功能显著升高，这种代偿性升高提示Tr可能发挥调节机体过度免疫反应的功能。

Objective To investigate the roles of regulatory T cells （Tr） in murine fulminant viral hepatitis （FVH） induced by routine hepatitis virus type 3 （ MHV-3 ） through detecting the proportions and cyto- kine production of Tr post MHV-3 infection. Methods The model of FVH was established by intraperitoneal injection of MHV-3 into BALB/cJ mice. The survival days of mice, the serum levels of alanine aminotransferase （ ALT）, aspartate aminotransferase （AST） and pathologic changes of liver tissues were examined. The proportions of Tr in blood, spleen and liver, as well as secretion of IL-10 in hepatic Tr were determined by flow cy- tometry. Results BALB/cJ mice died within 3 to 6 days after MHV-3 infection, with severe hepatic necrosis and significant augmentation of serum ALT and AST. The proportions of Tr significantly increased in the liver of BALB/cJ mice, meanwhile, the production of IL-10 in hepatic Tr and liver tissue remarkably increased. Conclusion The proportion and function of hepatic Tr compensatorily increased in MHV-3-induced FVH, suggesing its role in inhibiting the over-reaction of immune system in FVH.