Dendritic cells permit immune invasion of the CNS in an animal model of multiple sclerosis
Dendritic cells permit immune invasion of the CNS in an animal model of multiple sclerosis
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DOI：
10.1038/nm1197
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发表时间：
2005-03-01
期刊：
影响因子：
82.9
通讯作者：
Becher, B
中科院分区：
文献类型：
--
作者：
Greter, M;Heppner, FL;Becher, B
用髓鞘抗原进行免疫会导致实验性自身免疫性脑脊髓炎的发生，这是一种多发性硬化症的动物模型。该疾病也可通过将致脑炎的CD4(+) T辅助（TH）淋巴细胞转移到未免疫的小鼠体内而诱发。这些T细胞需要在主要组织相容性复合体（MHC）II类抗原呈递细胞（APCs）的环境下再次遇到它们的同源抗原，以便识别它们的靶标。介导T细胞进入中枢神经系统（CNS）的APC的细胞类型和位置仍然未知。在此，我们表明淋巴网状系统和中枢神经系统实质的APCs对于中枢神经系统的免疫侵袭是不必要的。我们还描述了在人脑组织中存在一群离散的血管相关树突状细胞（DCs）。在小鼠中，仅CD11c(+) DCs就足以在体内将抗原呈递给已致敏的髓鞘反应性T细胞，以介导中枢神经系统炎症和临床疾病的发展。
Immunization with myelin antigens leads to the development of experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. The disease can also be induced by the transfer of encephalitogenic CD4(+) T helper (TH) lymphocytes into naive mice. These T cells need to re-encounter their cognate antigen in the context of major histocompatibility complex (MHC) class II-bearing antigen-presenting cells (APCs) in order to recognize their target. The cell type and location of the APC mediating T-cell entry into the central nervous system (CNS) remain unknown. Here, we show that APCs of the lymphoreticular system and of the CNS parenchyma are dispensable for the immune invasion of the CNS. We also describe that a discrete population of vessel-associated dendritic cells (DCs) is present in human brain tissue. In mice, CD11c(+) DCs alone are sufficient to present antigen in vivo to primed myelin-reactive T cells in order to mediate CNS inflammation and clinical disease development.