Cutting Edge: Natalizumab Blocks Adhesion but Not initial Contact of Human T Cells to the Blood-Brain Barrier In Vivo in an Animal Model of Multiple Sclerosis
Cutting Edge: Natalizumab Blocks Adhesion but Not initial Contact of Human T Cells to the Blood-Brain Barrier In Vivo in an Animal Model of Multiple Sclerosis
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DOI：
10.4049/jimmunol.0803418
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发表时间：
2009-05-15
影响因子：
4.4
通讯作者：
Engelhardt, Britta
中科院分区：
文献类型：
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作者：
Coisne, Caroline;Mao, Wenxian;Engelhardt, Britta
人源化抗α 4整合素抗体Natalizumab是治疗复发缓解型多发性硬化症的有效药物。Natalizumab被认为通过阻断α（4）整合素介导的循环免疫细胞与血脑屏障（BBB）的结合来发挥其治疗功效。由于α（4）整合素控制其他免疫过程，但那他珠单抗可能在其他地方发挥其有益作用。通过活体显微镜检查，我们证明了那他珠单抗特异性抑制急性实验性自身免疫性脑脊髓炎（EAE）小鼠炎症BBB上人T细胞的牢固粘附，但不抑制其滚动或捕获。发现那他珠单抗阻断T细胞粘附至发炎的BBB的效率在EAE中比在急性全身性TNF-α诱导的炎症中更有效。我们的数据表明，在EA-E期间，α 4整合素介导的人T细胞与发炎的BBB的粘附被那他珠单抗有效地阻断，因此提供了多发性硬化症中这种疗法的概念的第一个直接体内证据。免疫学杂志，2009，182：5909-5913.
The humanized anti-alpha(4) integrin Ab Natalizumab is an effective treatment for relapsing-remitting multiple sclerosis. Natalizumab is thought to exert its therapeutic efficacy by blocking the alpha(4) integrin-mediated binding of circulating immune cells to the blood-brain barrier (BBB). As alpha(4) integrins control other immunological processes, natalizumab may, however, execute its beneficial effects elsewhere. By means of intravital microscopy we demonstrate that natalizumab specifically inhibits the firm adhesion but not the rolling or capture of human T cells on the inflamed BBB in mice with acute experimental autoimmune encephalomyelitis (EAE). The efficiency of natalizumab to block T cell adhesion to the inflamed BBB was found to be more effective in EAE than in acute systemic TNF-alpha-induced inflammation. Our data demonstrate that alpha(4) integrin-mediated adhesion of human T cells to the inflamed BBB during EA-E is efficiently blocked by natalizumab and thus provide the first direct in vivo proof of concept of this therapy in multiple sclerosis. The Journal of Immunology, 2009, 182: 5909-5913.