Greter Melanie, Heppner Frank L, Lemos Maria P, Odermatt Bernhard M, Goebels Norbert, Laufer Terri, Noelle Randolph J, Becher Burkhard
Neuroimmunology Unit, Department of Neurology, University Hospital Zurich, Frauenklinkstrasse 10, CH-8091 Switzerland.
Nat Med. 2005 Mar;11(3):328-34. doi: 10.1038/nm1197. Epub 2005 Feb 27.
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 (T(H)) 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.
用髓磷脂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+辅助性T（Th）淋巴细胞转移到未接触过抗原的小鼠体内诱导产生。这些T细胞需要在携带主要组织相容性复合体（MHC）II类分子的抗原呈递细胞（APC）的背景下再次遇到其同源抗原，以便识别其靶标。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。在这里，我们表明淋巴网状系统和CNS实质的APC对于CNS的免疫侵袭是可有可无的。我们还描述了在人类脑组织中存在离散的血管相关树突状细胞（DC）群体。在小鼠中，单独的CD11c+ DC足以在体内将抗原呈递给致敏的髓磷脂反应性T细胞，以介导CNS炎症和临床疾病的发展。
