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SJL 小鼠髓鞘少突胶质细胞糖蛋白 139-151 模拟表位诱导中枢神经系统自身免疫的性别差异。

Gender differences in CNS autoimmunity induced by mimicry epitope for PLP 139-151 in SJL mice.

机构信息

School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, United States.

出版信息

J Neuroimmunol. 2011 Jan;230(1-2):95-104. doi: 10.1016/j.jneuroim.2010.09.011. Epub 2010 Oct 15.

Abstract

Development of multiple sclerosis (MS) is more prevalent in females than in males, but the underlying mechanisms are not clear. Microbial infections have been suspected as triggers of MS and it is not known whether gender differences in reactivity to environmental antigens contribute to the disease pathogenesis. We demonstrated that ACA 83-95, a mimicry epitope from Acanthamoeba castellanii for proteolipid protein (PLP) 139-151, induces clinical signs of encephalomyelitis in both male and female SJL mice. Conversely ACA 83-95-induced effector cells from males fail to induce disease in female mice. Although we found no gender differences in the frequencies of antigen-specific cells including cytokine production, PLP-specific cells induced with ACA 83-95 differed in T cell receptor vβ usage from those induced with PLP 139-151. The data suggest that cross-reactive T cell expansion occurs similarly in both males and females, but their disease-inducing ability is influenced by gender.

摘要

多发性硬化症(MS)在女性中的发病率高于男性,但潜在机制尚不清楚。微生物感染被怀疑是 MS 的触发因素,目前尚不清楚对环境抗原反应的性别差异是否有助于疾病的发病机制。我们证明,来自棘阿米巴原虫的 ACA 83-95 模拟表位针对蛋白脂质蛋白(PLP)139-151,可诱导 SJL 雄性和雌性小鼠出现脑脊髓炎的临床症状。相反,来自雄性的 ACA 83-95 诱导的效应细胞无法在雌性小鼠中引发疾病。尽管我们没有发现抗原特异性细胞(包括细胞因子产生)的频率存在性别差异,但与用 PLP 139-151 诱导的细胞相比,用 ACA 83-95 诱导的 PLP 特异性细胞的 T 细胞受体 vβ 使用存在差异。这些数据表明,交叉反应性 T 细胞在男性和女性中均以相似的方式扩增,但它们的致病能力受到性别的影响。

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