An antigen-specific pathway for CD8 T cells across the blood-brain barrier.
An antigen-specific pathway for CD8 T cells across the blood-brain barrier.
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DOI：
10.1084/jem.20070064
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发表时间：
2007-09-03
期刊：
影响因子：
--
通讯作者：
Perry VH
中科院分区：
文献类型：
--
作者：
Galea I;Bernardes-Silva M;Forse PA;van Rooijen N;Liblau RS;Perry VH
CD8 T细胞是脑炎和脑肿瘤中自然界最重要的防御。抗原特异性CD8 T细胞需要进入大脑才能发挥其有益作用。另一方面，神经抗原特异性CD8 T细胞的运输可能引发自身免疫性疾病，如多发性硬化症。T细胞进入中枢神经系统被认为是在活化的T细胞穿过血脑屏障（BBB）时发生的，无论其抗原特异性如何，但研究集中在CD4 T细胞上。在这里，我们表明，选择性交通抗原特异性CD8 T细胞进入大脑中发生在体内，并依赖于管腔表达的主要组织相容性复合体（MHC）I类脑内皮细胞。在脑内抗原注射后，使用微创技术，转基因CD8 T细胞仅在其同源抗原存在时和存在处浸润脑。这与血管周围巨噬细胞的抗原呈递无关。静脉注射阻断性抗MHC I类抗体后，观察到抗原特异性CD8 T细胞浸润显著减少。这些结果暴露了迄今为止未被认识到的途径，通过该途径，CD8 T细胞归巢到BBB后面的其同源抗原上：脑内皮向循环CD8 T细胞的管腔MHC I类抗原呈递。这对多种疾病具有影响，其中抗原特异性CD8 T细胞进入大脑是有益或有害的特征。
CD8 T cells are nature's foremost defense in encephalitis and brain tumors. Antigen-specific CD8 T cells need to enter the brain to exert their beneficial effects. On the other hand, traffic of CD8 T cells specific for neural antigen may trigger autoimmune diseases like multiple sclerosis. T cell traffic into the central nervous system is thought to occur when activated T cells cross the blood-brain barrier (BBB) regardless of their antigen specificity, but studies have focused on CD4 T cells. Here, we show that selective traffic of antigen-specific CD8 T cells into the brain occurs in vivo and is dependent on luminal expression of major histocompatibility complex (MHC) class I by cerebral endothelium. After intracerebral antigen injection, using a minimally invasive technique, transgenic CD8 T cells only infiltrated the brain when and where their cognate antigen was present. This was independent of antigen presentation by perivascular macrophages. Marked reduction of antigen-specific CD8 T cell infiltration was observed after intravenous injection of blocking anti–MHC class I antibody. These results expose a hitherto unappreciated route by which CD8 T cells home onto their cognate antigen behind the BBB: luminal MHC class I antigen presentation by cerebral endothelium to circulating CD8 T cells. This has implications for a variety of diseases in which antigen-specific CD8 T cell traffic into the brain is a beneficial or deleterious feature.
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DOI：
10.1084/jem.20021378
发表时间：
2003-03-03
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Savinov AY;Wong FS;Stonebraker AC;Chervonsky AV
通讯作者：
Chervonsky AV
DOI：
10.1084/jem.192.3.393
发表时间：
2000-08-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Babbe H;Roers A;Waisman A;Lassmann H;Goebels N;Hohlfeld R;Friese M;Schröder R;Deckert M;Schmidt S;Ravid R;Rajewsky K
通讯作者：
Rajewsky K
影响因子：
3.3
作者：
Killestein, J;Eikelenboom, MJ;Polman, CH
通讯作者：
Polman, CH
影响因子：
20.3
作者：
Marelli-Berg, FM;James, MJ;Lechler, RI
通讯作者：
Lechler, RI
多发性硬化症模型中髓磷脂特异性CD8（+）T细胞的致病作用。
影响因子：
15.3
作者：
Huseby, E S;Liggitt, D;Brabb, T;Schnabel, B;Ohlen, C;Goverman, J
通讯作者：
Goverman, J