Lyck Ruth, Engelhardt Britta
Theodor Kocher Institute, University of Bern, Bern, Switzerland.
J Vasc Res. 2012;49(6):497-509. doi: 10.1159/000341232. Epub 2012 Aug 29.
During multiple sclerosis or its animal model, experimental autoimmune encephalomyelitis, circulating immune cells enter the central nervous system (CNS) causing neuroinflammation. Extravasation from the blood circulation across the vessel wall occurs through a multistep process regulated by adhesion and signal transducing molecules on the immune cells and on the endothelium. Since the CNS is shielded by the highly specialized blood-brain barrier (BBB), immune cell extravasation into the CNS requires breaching this particularly tight endothelial border. Consequently, travelling into the CNS demands unique adaptations which account for the extreme tightness of the BBB. Modern imaging tools have shown that after arresting on BBB endothelium, in vivo or in vitro encephalitogenic effector/memory T cells crawl for long distances, possibly exceeding 150 µm along the surface of the BBB endothelium before rapidly crossing the BBB. Interestingly, in addition to the distance of crawling, the preferred direction of crawling against the flow is unique for T cell crawling on the luminal surface of CNS microvessels. In this review, we will summarize the cellular and molecular mechanisms involved in the unique T cell behavior that is obviously required for finding a site permissive for diapedesis across the unique vascular bed of the BBB.
在多发性硬化症或其动物模型实验性自身免疫性脑脊髓炎中，循环免疫细胞进入中枢神经系统（CNS），引发神经炎症。免疫细胞从血液循环穿过血管壁外渗是一个多步骤过程，受免疫细胞和内皮细胞上的黏附及信号转导分子调控。由于中枢神经系统受到高度特化的血脑屏障（BBB）保护，免疫细胞渗入中枢神经系统需要突破这一特别紧密的内皮边界。因此，进入中枢神经系统需要独特的适应机制，这也解释了血脑屏障的极度紧密性。现代成像工具显示，在体内或体外，致脑炎性效应/记忆T细胞在血脑屏障内皮细胞上停滞之后，会沿血脑屏障内皮细胞表面远距离爬行，爬行距离可能超过150微米，然后迅速穿过血脑屏障。有趣的是，除了爬行距离外，T细胞在中枢神经系统微血管腔表面爬行时，逆血流方向的首选爬行方向也是独特的。在这篇综述中，我们将总结参与这种独特T细胞行为的细胞和分子机制，这种行为显然是在血脑屏障独特血管床中找到允许渗出的位点所必需的。
