Effective and selective immune surveillance of the brain by MHC class I-restricted cytotoxic T lymphocytes

被引:90
作者
Cabarrocas, J
Bauer, J
Piaggio, E
Liblau, R
Lassmann, H
机构
[1] Univ Vienna, Brain Res Inst, Div Neuroimmunol, A-1090 Vienna, Austria
[2] Hop La Pitie Salpetriere, INSERM, U546, Paris, France
[3] Hop La Pitie Salpetriere, Immunol Lab, Paris, France
关键词
cytotoxic T cell; CD8; MHC class I; brain inflammation; immune surveillance; central nervous system;
D O I
10.1002/eji.200323492
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Cytotoxic CD8(+) T cells are abundantly present in human virus-induced or putative autoimmune diseases of the central nervous system (CNS). Their direct role in the induction of inflammatory brain damage is, however, poorly understood. We have studied CD8(+) T cell-mediated brain inflammation by transferring MHC class I-restricted hemagglutinin (HA)-reactive T cells from a TCR transgenic mouse line into transgenic mice, which express HA in astrocytes. We show that activated CD8(+) T cells alone can induce monophasic brain inflammation in immunocompetent recipient animals. Similar to previous studies, involving transfer of CD4(+) cells, brain inflammation peaks after 5-7 days and then declines. The pathology of brain inflammation, however, differs fundamentally from that induced by CD4(+) cells. The inflammatory reaction is dominated by T cells and activated microglia in the virtual absence of hematogenous macrophages. This is associated with exquisitely specific destruction of antigen-containing astrocytes in the absence of any bystander damage of myelin, oligodendrocytes or neurons. Furthermore, in contrast to CD4(+) T cells, some CD8(+) cells accumulate in the brain and activate microglia in recipient animals, even in the absence of the specific antigen in the CNS. These data indicate that CD8(+) T cells are prime candidates for immune surveillance of the CNS.
引用
收藏
页码:1174 / 1182
页数:9
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