目的:探讨调节性T细胞在Polyinosinic-polycytidylic acid (poly I:C)/D-galactosamine (D-GalN) 诱发的急性肝脏损伤中的作用及其机制.方法:建立poly I:C/D-GalN诱发的爆发性肝炎小鼠模型,观察比较野生型C57BL/6小鼠、Rag1-/-小鼠(C57BL/6背景)和过继转输调节性 T细胞的Rag1-/-小鼠的血清转氨酶活性;肝脏HE染色评价小鼠肝组织病理形态学改变;实时荧光定量PCR检测肝脏TNF-α和IFN-γ mRNA水平;ELISA检测血清IFN-γ和TNF-α蛋白水平.结果:poly I:C/D-GalN联合注射后,与野生型小鼠相比,Rag1-/-小鼠血清转氨酶水平明显增高,肝脏损伤更加严重,炎性因子 mRNA水平和蛋白水平都显著增加.给Rag1-/-小鼠过继转输CD25+ 细胞后能明显降低poly I:C/D-GalN诱导的肝脏损伤.结论:调节性T细胞对poly I:C/D-GalN诱发的肝脏损伤有抑制作用,提示调节性T细胞可以负向调节天然免疫细胞.
Objective:To explore the role of regulatory T cells (Tregs) in liver injury induced by poly I: C/D-GaIN. Methods: In this study, C57BL/6 mice and Ragl-/- mice were injected with poly I: C/D-GaIN. Liver injury was evaluated by serum transaminase activity and histopathologic changes, mRNA levels of TNF-α and IFN-γ in the liver were measured by real time quantitative PCR, and their protein levels were determined by ELISA. Results: After injection of poly I:C/D-GalN, Ragl -/- mice showed higher ALT activity and more serious liver injury than C57BL/6 mice. And mRNA and protein levels of inflammatory cytokine were sig- nificantly increased in Ragl -/- mice. Transfer of CD25 + cells significantly reduced liver injury in poly I : C/D-GaiN-treated Ragl -/- mice. Conclusion: Tregs can suppress poly I: C/D-GaiN-induced liver injury, which indicates that Tregs may negatively regulate the response of natural immune cells.