Swift entry of myelin-specific T lymphocytes into the central nervous system in spontaneous autoimmune encephalomyelitis.

Swift entry of myelin-specific T lymphocytes into the central nervous system in spontaneous autoimmune encephalomyelitis.
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DOI:
10.4049/jimmunol.181.7.4648
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发表时间:
2008-10-01
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Lafaille JJ
Lafaille JJ
中科院分区:
其他
文献类型:
--
作者:
Furtado GC;Marcondes MC;Latkowski JA;Tsai J;Wensky A;Lafaille JJ

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强有力的证据支持CNS特异性CD 4 + T细胞是多发性硬化症和实验性自身免疫性脑脊髓炎(EAE)发病机制的核心。使用自发性EAE模型,我们证明了髓鞘碱性蛋白(MBP)特异性CD 4 + T细胞上调CNS引流颈淋巴结中的活化标志物,此时其他任何地方(包括CNS)均无T细胞活化,并且在出现临床体征之前。在自发性EAE中,MBP特异性T细胞的数量不会在CNS中逐渐增加;相反,产生IFN-γ的T细胞迅速迁移到CNS中,发生在EAE神经系统体征发作前约24小时。手术切除健康的前EAE转基因小鼠的颈部淋巴结,延迟了EAE的发病,并导致较轻的疾病。在用MBP/CFA免疫诱导的EAE中,在疾病之前注射部位的引流淋巴结中的T细胞的类似活化。综上所述,我们的结果表明引流淋巴结中T细胞的外周活化是EAE发展的早期事件,这为产生IFN-γ的CD 4 + T细胞最初爆发进入CNS铺平了道路。
Strong evidence supports that CNS-specific CD4+ T cells are central to the pathogenesis of multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). Using a model of spontaneous EAE, we demonstrated that myelin basic protein (MBP)-specific CD4+ T cells up-regulate activation markers in the CNS-draining cervical lymph nodes at a time when there is no T cell activation anywhere else, including the CNS, and before the appearance of clinical signs. In spontaneous EAE, the number of MBP-specific T cell numbers does not build up gradually in the CNS; instead, a swift migration of IFN-γ-producing T cells into the CNS takes place ~24 h before the onset of neurological signs of EAE. Surgical excision of the cervical lymph nodes in healthy pre-EAE transgenic mice delayed the onset of EAE and resulted in a less severe disease. In EAE induced by immunization with MBP/CFA, a similar activation of T cells in the draining lymph nodes of the injection site precedes the disease. Taken together, our results suggest that peripheral activation of T cells in draining lymph nodes is an early event in the development of EAE, which paves the way for the initial burst of IFN-γ-producing CD4+ T cell into the CNS.
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