Hofstetter Harald H, Toyka Klaus V, Tary-Lehmann Magdalena, Lehmann Paul V
Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.
J Immunol. 2007 Feb 1;178(3):1372-8. doi: 10.4049/jimmunol.178.3.1372.
In experimental autoimmune encephalomyelitis (EAE), the production of proinflammatory cytokines by neuroantigen-specific T cells is thought to initiate and maintain the inflammatory autoimmune pathology. Because gene knockout strategies have shown that IFN-gamma and TNF are not essential for EAE development, there is increasing interest in establishing the role of other proinflammatory cytokines, primarily IL-17 in EAE. We used an IL-17 ELISPOT assay to track the neuroantigen-specific IL-17-producing T cells at single-cell resolution in various organs of SJL mice undergoing PLP 139-151-induced EAE. Overall, the migration patterns and population kinetics of the PLP 139-151-specific IL-17-producing CD4 cells were reminiscent of the IFN-gamma-producing cells, with the exception of IL-17 producers far outnumbering the IFN-gamma and IL-2 producers in the inflamed CNS. The selective enrichment of IL-17-producing CD4 cells in the CNS is suggestive of the pathogenic role of an independent (non-Th1) IL-17-producing proinflammatory effector T cell class in EAE.
在实验性自身免疫性脑脊髓炎（EAE）中，神经抗原特异性T细胞产生促炎细胞因子被认为启动并维持炎症性自身免疫病理过程。由于基因敲除策略已表明干扰素-γ和肿瘤坏死因子对EAE的发展并非必不可少，因此人们越来越关注确定其他促炎细胞因子的作用，主要是白细胞介素-17在EAE中的作用。我们使用白细胞介素-17酶联免疫斑点分析（IL-17 ELISPOT），以单细胞分辨率追踪在经历髓鞘少突胶质细胞糖蛋白（PLP）139-151诱导的EAE的SJL小鼠的各种器官中产生神经抗原特异性白细胞介素-17的T细胞。总体而言，产生PLP 139-151特异性白细胞介素-17的CD4细胞的迁移模式和群体动力学让人联想到产生干扰素-γ的细胞，不同的是，在发炎的中枢神经系统中，产生白细胞介素-17的细胞数量远远超过产生干扰素-γ和白细胞介素-2的细胞。中枢神经系统中产生白细胞介素-17的CD4细胞的选择性富集表明，在EAE中存在一类独立的（非Th1）产生白细胞介素-17的促炎效应T细胞具有致病作用。
