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

在本报告中，我们比较了氟烷处理后正常雌性Balb/cJ小鼠和缺乏调节性T细胞的Balb/cJ小鼠的适应性免疫反应。与正常的Balb/cJ小鼠相比，调节性T细胞缺失的小鼠在tfa蛋白加合物培养下，血清抗tfa蛋白抗体水平显著提高，T细胞增殖水平显著提高。此外，在氟烷处理后，正常Balb/cJ小鼠的肝脏中有大量产生tgf - β的T调节细胞浸润。这些结果表明，T调节细胞可能对受损肝细胞释放的药物的蛋白质加合物的适应性免疫系统反应和对肝脏的免疫病理具有重要的抑制作用。

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.