Chronological changes of CD4(+) and CD8(+) T cell subsets in the experimental autoimmune encephalomyelitis, a mouse model of multiple sclerosis.
Chronological changes of CD4(+) and CD8(+) T cell subsets in the experimental autoimmune encephalomyelitis, a mouse model of multiple sclerosis.
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DOI：
10.1620/tjem.213.329
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发表时间：
2007-12
期刊：
影响因子：
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通讯作者：
Yoshifumi Sonobe;Shijie Jin;Jinyan Wang;J. Kawanokuchi;H. Takeuchi;T. Mizuno;A. Suzumura
中科院分区：
文献类型：
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作者：
Yoshifumi Sonobe;Shijie Jin;Jinyan Wang;J. Kawanokuchi;H. Takeuchi;T. Mizuno;A. Suzumura
多发性硬化（MS）是中枢神经系统（CNS）的炎性疾病。MS的病因尚不清楚，但对髓鞘组分（例如髓鞘少突胶质细胞糖蛋白（MOG））具有特异性的T细胞被认为在MS的发病中起关键作用。实验性自身免疫性脑脊髓炎（EAE）已被用作MS的动物模型，并且T辅助1型（Th 1）细胞通过产生Th 1细胞因子在EAE的发病机制中起重要作用，干扰素-γ（IFN-γ）和肿瘤坏死因子-α（TNF-α）。我们检测了用MOG肽（35-55个氨基酸残基）免疫EAE小鼠产生的脾脏和CNS中的CD 4（+）和CD 8（+）T细胞应答。CNS中CD 4（+）和CD 8（+）T细胞的数量及其MOG反应性与疾病严重程度的增加相关，但与脾脏中的那些无关，这表明CNS中MOG特异性CD 4（+）和CD 8（+）T细胞参与了EAE的发展。聚合酶链反应分析表明，CD 4（+）和CD 8（+）T细胞都产生IFN-γ和TNF-α，而CD 4（+）T细胞也产生白细胞介素-17（IL-17），这是EAE发生的一个重要因素。因此，CD 4（+）T细胞可能通过产生IL-17而参与EAE的诱导。此外，CD 8（+）T细胞表达更高水平的抑制性细胞因子IL-10。综上所述，我们的数据表明，CD 4（+）T细胞参与了EAE的早期阶段，而CD 8（+）T细胞在EAE的晚期阶段具有调节作用。
Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS). The etiology of MS remains unclear, but T cells specific for myelin components, such as myelin oligodendrocyte glycoprotein (MOG), are thought to play a critical role in the onset of MS. Experimental autoimmune encephalomyelitis (EAE) has been used as an animal model of MS, and T helper type 1 (Th1) cells play an essential role for the pathogenesis of EAE through the production of Th1 cytokines, interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha). We examined CD4(+) and CD8(+) T cell responses in the spleen and CNS of EAE mice, generated by immunization with a peptide (35-55 amino acid residues) of MOG. The number of both CD4(+) and CD8(+) T cells and their MOG-reactivity in the CNS were associated with increasing disease severity but not those in the spleen, suggesting that the MOG-specific CD4(+) and CD8(+) T cells in the CNS are involved in the development of EAE. Polymerase chain reaction analysis suggested that both CD4(+) and CD8(+) T cells produced IFN-gamma and TNF-alpha, while CD4(+) T cells also produced interleukin-17 (IL-17), an important factor in the development of EAE. Thus, CD4(+) T cells may contribute to the induction of EAE by producing IL-17. Furthermore, CD8(+) T cells express higher levels of a suppressive cytokine, IL-10. Taking together, our data suggest that CD4(+) T cells are involved in the early phase of EAE, whereas CD8(+) T cells have a regulatory role in the later stage of EAE.