A critical role for B7/CD28 costimulation in experimental autoimmune encephalomyelitis: A comparative study using costimulatory molecule-deficient mice and monoclonal antibody blockade
A critical role for B7/CD28 costimulation in experimental autoimmune encephalomyelitis: A comparative study using costimulatory molecule-deficient mice and monoclonal antibody blockade
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DOI：
10.4049/jimmunol.164.1.136
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发表时间：
2000-01-01
影响因子：
4.4
通讯作者：
Miller, SD
中科院分区：
文献类型：
--
作者：
Girvin, AR;Dal Canto, PC;Miller, SD
B7/CD28通路提供完全T细胞激活所需的关键共刺激信号，并已作为调节自身免疫性疾病的免疫治疗策略的潜在靶点。本研究旨在研究CD28及其单个配体B7-1和B7-2在实验性自身免疫性脑脊髓炎（EAE）中的作用，这是一种th1介导的中枢神经系统炎症性疾病，我们比较了CD28或B7缺乏的非肥胖糖尿病（NOD）小鼠对EAE的诱导，以及在野生型NOD小鼠中使用抗体阻断B7/CD28的效果。疾病严重程度显著降低在CD28-deficient anti-B7-1 / B7-2-treated点头老鼠,B7-2似乎扮演更重要的角色,有一个适度的减少疾病发生率和严重程度B7-2-deficient动物,运算单元电阻并不是由于缺乏有效的启动的髓磷脂peptide-specific体内T细胞,T细胞分离CD28-deficient动物产生等量的IFN-gamma和tnf的免疫原,事实上，在B7-1和b7 -2缺陷NOD小鼠中，ag特异性T细胞产生的ifn - γ和tnf - α增强，相反，这些动物的肽特异性延迟型超敏反应显著减少，提示CD28共刺激在体内运输和全身免疫中起关键作用。总之，这些结果支持CD28共刺激在EAE诱导中的关键作用。
The B7/CD28 pathway provides critical costimulatory signals required for complete T cell activation and has served as a potential target for immunotherapeutic strategies designed to regulate autoimmune diseases. This study was designed to examine the roles of CD28 and its individual ligands, B7-1 and B7-2, in experimental autoimmune encephalomyelitis (EAE), a Th1-mediated inflammatory disease of the CNS, EAE induction in CD28- or B7-deficient nonobese diabetic (NOD) mice was compared with the effects of B7/CD28 blockade using Abs in wild-type NOD mice. Disease severity was significantly reduced in CD28-deficient as well as anti-B7-1/B7-2-treated NOD mice, B7-2 appeared to play the more dominant role as there was a moderate decrease in disease incidence and severity in B7-2-deficient animals, EAE resistance was not due to the lack of effective priming of the myelin peptide-specific T cells in vivo, T cells isolated from CD28-deficient animals produced equivalent amounts of IFN-gamma and TNF-alpha in response to the immunogen, proteolipid protein 56-70, In fact, IFN-gamma and TNF-alpha production by Ag-specific T cells was enhanced in both the B7-1 and B7-2-deficient NOD mice, In contrast, peptide-specific delayed-type hypersensitivity responses in these animals were significantly decreased, suggesting a critical role for CD28 costimulation in in vivo trafficking and systemic immunity. Collectively, these results support a critical role for CD28 costimulation in EAE induction.