山东大学学报 (医学版) ›› 2023, Vol. 61 ›› Issue (10): 1-8.doi: 10.6040/j.issn.1671-7554.0.2023.0196
• 基础医学 • 下一篇
黎良康1,司伟岳1,吴兴原2,周阳2,魏舒丽1,董晶2,李晓丽1,2,段瑞生1,2
LI Liangkang1, SI Weiyue1, WU Xingyuan2, ZHOU Yang2, WEI Shuli1, DONG Jing2, LI Xiaoli1,2, DUAN Ruisheng1,2
摘要: 目的 探究实验性自身免疫性重症肌无力(EAMG)合并急性感染时免疫细胞的改变及其功能特征。 方法 利用大鼠乙酰胆碱受体(AChR)α亚基的97-116(R97-116)肽段免疫6~8周龄雌性Lewis大鼠,发病高峰期腹腔注射脂多糖(LPS)诱导急性感染模型为LPS组,腹腔注射PBS作为对照(PBS组)。记录临床评分及体质量。流式细胞术检测外周循环和淋巴器官中Th1、Th17、Treg细胞的比例以及脾脏滤泡辅助T细胞(Tfh)、树突状细胞(DC)、生发中心B细胞(GCB)的比例和功能。对脾脏分别进行PNA及CD4、Foxp3免疫荧光检测。采用酶联免疫吸附实验(ELISA)检测血清抗R97-116 IgG抗体及亚型水平。 结果 与PBS组相比,LPS组大鼠临床症状较重、体质量减轻,脾脏Treg细胞(CD4+CD25+)比例(P=0.016)及Foxp3的表达均明显减少。另外,LPS组大鼠脾脏PNA的表达增多且呈簇状,且GCB细胞表达MHC-Ⅱ及分泌IL-6的比例明显增加(P=0.002、P=0.017)。LPS组大鼠DC亚群表达CD80的平均荧光素强度(MFI)增加,但无统计学差异(P=0.057)。LPS组大鼠外周血免疫球蛋白G(IgG)水平无变化,保护性抗体IgG1水平降低(P=0.005),致病性抗体IgG2b水平无变化,IgG1/IgG2b下调(P=0.018)。 结论 LPS可能通过减少脾脏Treg细胞的比例及Foxp3的表达,增强脾脏生发中心反应、GCB细胞的功能以及DC亚群共刺激的能力来下调保护性抗体水平,最终导致EAMG大鼠的临床症状加重。
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