Dendritic cells permit immune invasion of the CNS in an animal model of multiple sclerosis

被引:685
作者
Greter, M
Heppner, FL
Lemos, MP
Odermatt, BM
Goebels, N
Laufer, T
Noelle, RJ
Becher, B
机构
[1] Univ Zurich Hosp, Dept Neurol, Neuroimmunol Unit, CH-8091 Zurich, Switzerland
[2] Univ Zurich Hosp, Dept Pathol, Inst Neuropathol, CH-8091 Zurich, Switzerland
[3] Univ Penn, Div Rheumatol, Philadelphia, PA 19104 USA
[4] Univ Zurich Hosp, Dept Pathol, Inst Clin Pathol, CH-8091 Zurich, Switzerland
[5] Dartmouth Coll Sch Med, Dept Microbiol & Immunol, Lebanon, NH 03755 USA
关键词
D O I
10.1038/nm1197
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:328 / 334
页数:7
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