【摘要】 目的探讨白细胞介素(IL)-10基因修饰的未成熟树突状细胞(iDC)对实验性自身免疫性心肌炎的作用。方法从Lewis大鼠骨髓培养成熟树突状细胞(mDC)和iDC,pcDNA3-IL-10质粒转染iDC。分别将2×106 mDC、iDC、pcDNA3-iDC、pcDNA3-IL-10-iDC或PBS回输5天前以猪心肌肌球蛋白免疫的实验性自身免疫性心肌炎大鼠体内。3周后观察心肌炎症、超声心动图、Th1/Th2细胞因子、主要组织相容性Ⅱ(MHC-Ⅱ)类分子及共刺激分子表达。以T细胞增殖实验及过继转移实验检测pcDNA3-IL-10-iDC诱导耐受的抗原特异性。结果IL-10基因修饰的iDC显著抑制抗原特异性T细胞增殖,pcDNA3-IL-10-iDC治疗后实验性自身免疫性心肌炎大鼠心肌炎症显著减轻,心功能改善,MHC-Ⅱ、共刺激分子表达显著降低,脾细胞分泌细胞因子呈Th2型。结论IL-10基因修饰的iDC可诱导实验性自身免疫性心肌炎产生抗原特异性耐受,其机制与IL-10诱导的Th1/Th2偏离及MHC-Ⅱ、共刺激分子表达下调等有关。更多还原

【Abstract】 Objective To investigate whether IL-10 gene modification on immature dendritic cells (iDC) could induce autoimmune tolerance in rat experimental autoimmune myocarditis(EAM).Methods EAM was induced by cardiac myosin immunization on day 0 and day 7 in rats.A total of 2×106 mature DC (mDC),iDC,pcDNA3 transfected iDC,pcDNA3-IL-10 transfected iDC or PBS were injected intravenously at 5th immunization day. Three weeks later,echocardiography and HE staining were performed to observe the cardiac function and myocardial inflammation. Th1/Th2 cytokines were detected by ELISA and MHC-Ⅱmolecules,costimulatory molecules were identified by flow cytometry. In vitro T lymphocyte proliferation assay and adoptive transfer of DCs were performed to determine the antigen specific tolerance induced by IL-10 gene modification on iDCs. Results EAM rats treated with pcDNA3-IL-10 transfected iDC showed improved cardiac function and reduced inflammatory cells infiltration into myocardium. Moreover,lower Th1 and higher Th2-type response was induced, MHC-Ⅱand costimulatory molecules down-regulated and antigen specific immunological responses towards cardiac myosin inhibited in pcDNA3-IL-10-iDC treated EAM rats. Conclusion Treatment with IL-10 gene modified iDCs could ameliorates EAM by inducing Th2 polarization and down-regulation of MHC-Ⅱmolecules and costimulatory molecule expressions.更多还原