Role of Innate and Adaptive Immune Systems in Drug-Induced Liver Disease

在这份报告中，我们比较了正常雌性Balb/CJ小鼠和缺乏调节性T细胞的Balb/CJ小鼠在氟烷治疗后的适应性免疫反应。与正常Balb/CJ小鼠相比，与正常Balb/CJ小鼠相比，缺乏调节性T细胞的小鼠在用TFA蛋白加合物培养时，血清中抗TFA蛋白抗体水平显著升高，T细胞增殖能力增强。此外，氟烷治疗后，正常Balb/CJ小鼠肝脏中有大量产生转化生长因子-β的T调节细胞。这些结果提示，T调节细胞可能对适应性免疫系统对受损肝细胞释放的药物蛋白加合物的反应和对肝脏的免疫病理具有重要的抑制作用。 结论：这些初步发现值得进一步研究调节性T细胞在DILD发病机制和易感性中的作用。

In this report, we compared the adaptive immune responses following halothane treatment of normal female Balb/cJ mice to Balb/cJ mice depleted of regulatory T cells. Mice depleted of regulatory T cells had significantly higher serum levels of anti-TFA-protein antibodies and elevated T cell proliferation when treated in culture with TFA-protein adducts as compared to normal Balb/cJ mice. Moreover, there was a significant infiltration of TGF-beta-producing T regulatory cells into the liver of normal Balb/cJ mice following halothane treatment. These results suggest that T regulatory cells may have an important inhibitory effect on the adaptive immune system reaction against protein adducts of drugs released from damaged hepatocytes and immunopathology against the liver. Conclusion: These preliminary findings warrant further studies into the role of regulatory T cells in the mechanisms and susceptibility to DILD.