目的探讨负载乙酰胆碱受体(AChR)的未成熟树突状细胞(iDC)对实验性自身免疫性重症肌无力(EAMG)大鼠细胞因子表达的影响。方法30只雌性Lewis大鼠随机分为EAMG组、iDC组、成熟DC(mDC)组、负载AChR的iDC(AChR+iDC)组、负载AChR的mDC(AChR+mDC)组和正常对照组。分别给各组大鼠皮下注射培养基、iDC、mDC、AChR+iDC、AChR+mDC,正常对照组大鼠不注射。3周后给各组大鼠(除正常对照组)用AChR二次免疫法制作EAMG模型。免疫后每周进行EAMG症状评分,免疫7周后检测大鼠T细胞干扰素(IFN)-γ、白介素(IL)-12、IL-10和转化生长因子(TGF)-β1的表达水平。结果EAMG组、iDC组、mDC组和AChR+mDC组大鼠均产生了典型的MG症状;与正常对照组比较,其T细胞IFN-γ、IL-12、IL-10和TGF—β1的表达水平均显著增高(均P〈0.01)。AChR+iDC组仅有一只大鼠出现轻微MG症状,其IFN-γ和IL-12表达水平与正常对照组比较差异无统计学意义,IL—10和TGF-β1的表达水平均明显高于正常对照组(均P〈0.01),且TGF—B1的表达显著高于EAMG组、iDC组、mDC组和AChR+mDC组(均P〈0.05)。结论负载AChR的iDC能抑制EAMG大鼠细胞因子IFN-γ和IL-12表达,上调IL-10和TGF—β1表达,可能与其诱导EAMG耐受作用有关。
Objective To investigate the effect of immature dendritic cells (iDC) pulsed acetylcholine receptor (AChR) on expression of cytokines in rats with experimental autoimmune myasthenia gravis (EAMG). Methods 30 fmale Lewis rats were randomly divided into EAMG group, iDC group, mature DC (mDC) group, iDC pulsed AChR (AChR + iDC) group, mDC plused AChR (AChR + mDC) group and normal control group. Rats in each group were subcutaneous ingected with medium, iDC, mDC, AChR + iDC or AChR + mDC respectively, while the normal control group were not vaccinated. After 3 weeks, the EAMG modes were induced by AChR twice immunization method in each group except the normal control group. After 7 weeks of the immunization, the expression of interferon (IFN) - γ, interleukin (IL)-12, IL-10 and transforming growth factor (TGF)-1β of rats T cells were measured. Results The rats of EAMG group, iDC group, mDC group and AChR + mDC group showed typical symptoms of EAMG, and compared with normal control group, the expression of IFN-γ, IL-12, IL-10 and TGF-1β of T cells were significantly increased ( all P 〈 0. 01 ). There was 1 rat in AChR + iDC group showed only mild symptoms of EAMG. There were no significant differences of expression of IFN-3, and IL-12 between the AChR + iDC group and normal control group. But the expression of IL-10 and TGF-1β in AChR + iDC group were significantly higher than normal control group ( all P 〈 0.01 ). The expression of TGF-1β in AChR + iDC group were significantly higher than those in EAMG group, iDC group, mDC group and AChR + mDC group ( all P 〈 0.05). Conclusions iDC pulsed AChR can inhibite the expression of IFN-γ and IL-12, and regulate the expression of IL-10 and TGF-1β in EAMG rats. That may be related to induce the EAMG tolerance.