CAJ | 학술논문

目的：探讨自身免疫调节因子（autoimmune regulator ，AIRE）在实验性自身免疫性重症肌无力（ex‐perimental autoimmune myasthenia gravis ，EAMG）模型小鼠发病中的作用。方法采用亲和层析法从电鳐电器官中提取和纯化乙酰胆碱受体（acetylcholine receptor ，AChR），并用其免疫 C57BL／6小鼠，根据临床症状及重复电刺激试验结果将造模小鼠分为成模组及未成模组，检测各组小鼠胸腺内 AIRE mRNA 、AChRα1 mRNA 表达水平以及 CD4＋ CD25＋调节性 T 细胞（Treg）比例和胸腺细胞增殖能力，并与未成模组、福氏佐剂对照组及健康对照组进行比较。结果与未成模组、福氏佐剂对照组及健康对照组相比，成模组小鼠胸腺内 AChRα1亚基基因表达水平减少（P＜0.01），胸腺内 AIRE mRNA 表达水平明显下降（P＜0.01），胸腺内 CD4＋ T 细胞水平无统计学变化（P＞0.05），而胸腺内 Treg 与 CD4＋ T 细胞水平的比例却明显下降（P＜0.01），胸腺细胞对刀豆球蛋白A（ConA）刺激的增殖能力增强（P＜0.01）。结论 EAMG 小鼠模型存在中枢耐受缺陷，AIRE 基因通过调节胸腺异位基因的表达和 Treg 细胞比例而在 EAMG 的发病中起作用。
목적：탐토자신면역조절인자（autoimmune regulator ，AIRE）재실험성자신면역성중증기무력（ex‐perimental autoimmune myasthenia gravis ，EAMG）모형소서발병중적작용。방법채용친화층석법종전요전기관중제취화순화을선담감수체（acetylcholine receptor ，AChR），병용기면역 C57BL／6소서，근거림상증상급중복전자격시험결과장조모소서분위성모조급미성모조，검측각조소서흉선내 AIRE mRNA 、AChRα1 mRNA 표체수평이급 CD4＋ CD25＋조절성 T 세포（Treg）비례화흉선세포증식능력，병여미성모조、복씨좌제대조조급건강대조조진행비교。결과여미성모조、복씨좌제대조조급건강대조조상비，성모조소서흉선내 AChRα1아기기인표체수평감소（P＜0.01），흉선내 AIRE mRNA 표체수평명현하강（P＜0.01），흉선내 CD4＋ T 세포수평무통계학변화（P＞0.05），이흉선내 Treg 여 CD4＋ T 세포수평적비례각명현하강（P＜0.01），흉선세포대도두구단백A（ConA）자격적증식능력증강（P＜0.01）。결론 EAMG 소서모형존재중추내수결함，AIRE 기인통과조절흉선이위기인적표체화 Treg 세포비례이재 EAMG 적발병중기작용。
Objective To study the effects of autoimmune regulator factors on the mechanisms of central tolerance disorder in experimental autoimmune myasthenia gravis (EAMG) mice .Methods Acetylcholine receptor (AChR) was purified from the electric organs of Torpedo by affinity chromatography ,and was used to immunize C57BL /6 mice .The mice were divided into myasthenia gravis (MG ) symptom group and non MG symptom group by clinical manifestation and repetitive nerve stimulation . The level of CD4 + CD25 + Treg in thymus ,non‐specific proliferation of thymocytes stimulated with concanavalin A (ConA) ,mRNA expression of self‐antigen AChR α1 subunit and autoimmune regulator (AIRE) in the thymus of EAMG mice were tested and compared with those of other groups .Results Compared with non MG symptom group ,CFA group and control group , the level of CD4 + T cells in thymus of MG symptom group was not changed (P> 0.05) ,while the level of CD4 + CD25 + thymocytes in CD4 + cells decreased distinctly ( P < 0.01 ) . In the MG symptom group , the proliferation of thymocytes stimulated with ConA increased significantly , the mRNA expression of AChR α1 subunit and AIRE in thymus decreased dramatically (all P < 0.01) .Conclusions EAMG mice are deficient in central tolerance ,which is related with the development of MG .The blockade of thymic selection of autoreactive T cells and CD4 + CD25 + Treg is caused by the diminished expression of self‐antigen in thymus of EAMG mice .It also was the potential cause for the deficiency of central and peripheral tolerance .The decreased expression of AIRE in thymus of EAMG mice is the potential cause for the lower expression of self‐antigen in thymus .