Antigen recognition detains CD8(+) T cells at the blood-brain barrier and contributes to its breakdown.
Antigen recognition detains CD8(+) T cells at the blood-brain barrier and contributes to its breakdown.
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DOI：
10.1038/s41467-023-38703-2
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发表时间：
2023-05-30
影响因子：
16.6
通讯作者：
Engelhardt, Britta
中科院分区：
文献类型：
--
作者：
Aydin, Sidar;Pareja, Javier;Schallenberg, Vivianne M.;Klopstein, Armelle;Gruber, Thomas;Page, Nicolas;Bouillet, Elisa;Blanchard, Nicolas;Liblau, Roland;Koerbelin, Jakob;Schwaninger, Markus;Johnson, Aaron J.;Schenk, Mirjam;Deutsch, Urban;Merkler, Doron;Engelhardt, Britta
血脑屏障（BBB）的破坏和免疫细胞浸润到中枢神经系统（CNS）是多发性硬化（MS）的早期标志。在MS病变中发现大量的CD8+ T细胞，并且已经提出在BBB处的抗原（Ag）呈递促进CD8+ T细胞进入CNS。在这里，我们表明，脑内皮细胞的过程和交叉目前银，导致效应CD8+ T细胞分化。在体外生理血流条件下，内皮细胞Ag呈递阻止了CD8+ T细胞的爬行和渗出，导致脑内皮细胞凋亡和BBB破坏。由于CNS驻留巨噬细胞对Ag的摄取，体内脑内皮Ag呈递受到限制，但CNS微血管内Ag特异性CD8+ T细胞的运动性仍然降低。因此，在神经炎症期间，在BBB处的MHC I类限制性Ag呈递阻止了CD8+ T细胞进入CNS并触发了CD8+ T细胞介导的局灶性BBB破坏。血脑屏障（BBB）破坏和免疫细胞浸润到中枢神经系统是多发性硬化症的早期标志。在这里，作者证明了脑内皮细胞交叉呈递抗原给CD8+ T细胞，从而阻止它们的迁移并启动BBB破坏。
Blood-brain barrier (BBB) breakdown and immune cell infiltration into the central nervous system (CNS) are early hallmarks of multiple sclerosis (MS). High numbers of CD8+ T cells are found in MS lesions, and antigen (Ag) presentation at the BBB has been proposed to promote CD8+ T cell entry into the CNS. Here, we show that brain endothelial cells process and cross-present Ag, leading to effector CD8+ T cell differentiation. Under physiological flow in vitro, endothelial Ag presentation prevented CD8+ T cell crawling and diapedesis resulting in brain endothelial cell apoptosis and BBB breakdown. Brain endothelial Ag presentation in vivo was limited due to Ag uptake by CNS-resident macrophages but still reduced motility of Ag-specific CD8+ T cells within CNS microvessels. MHC class I-restricted Ag presentation at the BBB during neuroinflammation thus prohibits CD8+ T cell entry into the CNS and triggers CD8+ T cell-mediated focal BBB breakdown. Blood-brain barrier (BBB) breakdown and immune cell infiltration into the central nervous system are early hallmarks of multiple sclerosis. Here, the authors demonstrate that brain endothelial cells cross-present antigen to CD8+ T cells, thereby preventing their migration and initiating BBB breakdown.
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影响因子：
64.8
作者：
Drieu, Antoine;Du, Siling;Storck, Steffen E.;Rustenhoven, Justin;Papadopoulos, Zachary;Dykstra, Taitea;Zhong, Fenghe;Kim, Kyungdeok;Blackburn, Susan;Mamuladze, Tornike;Harari, Oscar;Karch, Celeste M.;Bateman, Randall J.;Perrin, Richard;Farlow, Martin;Chhatwal, Jasmeer;Hu, Song;Randolph, Gwendalyn J.;Smirnov, Igor;Kipnis, Jonathan
通讯作者：
Kipnis, Jonathan
影响因子：
64.8
作者：
Alam, SM;Travers, PJ;Gascoigne, NRJ
通讯作者：
Gascoigne, NRJ
DOI：
10.1084/jem.20070064
发表时间：
2007-09-03
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Galea I;Bernardes-Silva M;Forse PA;van Rooijen N;Liblau RS;Perry VH
通讯作者：
Perry VH
影响因子：
5.4
作者：
Abadier, Michael;Jahromi, Neda Haghayegh;Lyck, Ruth
通讯作者：
Lyck, Ruth
影响因子：
7.2
作者：
Dustin, Michael L.
通讯作者：
Dustin, Michael L.