Xiaoyan Zhao, Pirskanen R, Malmstrom V, Lefvert A K
Immunological Research Unit, Centre for Molecular Medicine and Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
Clin Exp Immunol. 2006 Jan;143(1):110-6. doi: 10.1111/j.1365-2249.2005.02955.x.
Myasthenia gravis (MG) is commonly regarded as the prototype of an antibody-mediated, organ-specific autoimmune disease. Antibodies against the acetylcholine receptor (AChR) on the muscle endplate trigger its typical clinical manifestations of weakness and fatiguability. T-B cell interactions are thought to play a crucial role in the pathogenesis of MG. OX40 (CD134), a costimulatory molecule that is expressed on activated CD4+ T-cells, might contribute to the development or pathogenesis of immune-mediated diseases such as rheumatoid arthritis and graft-versus-host disease. In the present study, we investigated the expression of OX40 on CD4+ T-cells from patients with MG and healthy individuals. Results from 36 MG patients and 28 healthy controls revealed that more freshly isolated CD4+ T-cells from MG patients expressed OX40 than cells from healthy individuals. High levels of antibodies against the AChR, thymic hyperplasia and onset at an early age were associated with elevated expression of OX40. Upon activation by various concentrations of anti-CD3 antibodies, CD4+ T-cells from MG patients showed a tendency toward higher levels of OX40 expression than cells from healthy individuals. Given the role of OX40 in the immune system, we conclude that OX40 might contribute to the development of MG.
重症肌无力(MG)通常被视为抗体介导的器官特异性自身免疫性疾病的典型代表。针对肌肉终板上乙酰胆碱受体(AChR)的抗体引发其典型的肌无力和易疲劳的临床表现。T细胞与B细胞的相互作用被认为在MG的发病机制中起关键作用。OX40(CD134)是一种在活化的CD4 + T细胞上表达的共刺激分子,可能在诸如类风湿性关节炎和移植物抗宿主病等免疫介导疾病的发展或发病机制中发挥作用。在本研究中,我们调查了MG患者和健康个体的CD4 + T细胞上OX40的表达情况。36例MG患者和28例健康对照的结果显示,与健康个体的细胞相比,MG患者中更多新鲜分离的CD4 + T细胞表达OX40。抗AChR抗体水平高、胸腺增生以及发病年龄早与OX40表达升高有关。在用不同浓度的抗CD3抗体激活后,MG患者的CD4 + T细胞比健康个体的细胞表现出更高水平的OX40表达趋势。鉴于OX40在免疫系统中的作用,我们得出结论,OX40可能在MG的发展中起作用。