Biernacki K, Prat A, Blain M, Antel J P
Neuroimmunology Unit, Montreal Neurological Institute, McGill University, Quebec, Canada.
J Neuropathol Exp Neurol. 2001 Dec;60(12):1127-36. doi: 10.1093/jnen/60.12.1127.
Endothelial cells of the blood-brain barrier (BBB) have the ability to regulate and restrict the passage of cells and molecules from the periphery to the CNS. We have used an in vitro assay of lymphocyte migration across monolayers of human adult brain endothelial cells (HBEC) as a model of lymphocyte migration across the BBB. We found that human allogeneic or MBP-reactive Th2-polarized lymphocytes migrate more avidly than Th1-polarized lymphocytes. Migration of Th2 but not Th1 cells across brain endothelium was inhibited by antibodies directed at MCP-1, a chemokine produced by HBECs. We could detect CCR2, a chemokine receptor that recognizes MCP-1 on Th2 but not Th1 lymphocytes. ICAM-1 and VCAM-1 molecules were expressed on the surface of HBECs under basal conditions and were upregulated by Th1 but not Th2 cell-derived supernatants. Migration of both lymphocyte subsets was dependent on LFA-1/ICAM-1 interactions. Blocking VLA-4/VCAM-1 binding did not influence actual trans-endothelial migration. These results suggest that HBECs composing the BBB favor the migration of Th2 cells. We postulate that this selectivity may help prevent activated Th1 lymphocytes, the putative CNS autoimmune disease initiating cells, from reaching the CNS parenchyma and favor entry of Th2 cells, a putative means to induce bystander suppression in the CNS.
血脑屏障（BBB）的内皮细胞能够调节并限制细胞和分子从外周进入中枢神经系统（CNS）。我们采用人成年脑内皮细胞（HBEC）单层上淋巴细胞迁移的体外检测方法，作为淋巴细胞穿越血脑屏障迁移的模型。我们发现，人异体或髓鞘碱性蛋白（MBP）反应性Th2极化淋巴细胞比Th1极化淋巴细胞迁移更活跃。针对单核细胞趋化蛋白-1（MCP-1，一种由HBEC产生的趋化因子）的抗体可抑制Th2细胞而非Th1细胞穿越脑内皮的迁移。我们能够检测到CCR2，一种在Th2而非Th1淋巴细胞上识别MCP-1的趋化因子受体。ICAM-1和VCAM-1分子在基础条件下表达于HBEC表面，并被Th1而非Th2细胞来源的上清液上调。两个淋巴细胞亚群的迁移均依赖于LFA-1/ICAM-1相互作用。阻断VLA-4/VCAM-1结合并不影响实际的跨内皮迁移。这些结果表明，构成血脑屏障的HBEC有利于Th2细胞的迁移。我们推测，这种选择性可能有助于防止作为假定的中枢神经系统自身免疫性疾病起始细胞的活化Th1淋巴细胞到达中枢神经系统实质，并有利于Th2细胞进入，这是在中枢神经系统中诱导旁观者抑制的一种假定方式。
