The development of experimental autoimmune encephalomyelitis in the mouse requires α4-integrin but not α4β7-integrin
The development of experimental autoimmune encephalomyelitis in the mouse requires α4-integrin but not α4β7-integrin
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DOI：
10.1172/jci4271
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发表时间：
1998-12-15
影响因子：
15.9
通讯作者：
Hoch, G
中科院分区：
文献类型：
--
作者：
Engelhardt, B;Laschinger, M;Hoch, G
由于针对α 4-整联蛋白和VCAM-1的单克隆抗体（mAb）在体内抑制实验性自身免疫性脑脊髓炎（EAE）的发展，因此已经得出结论，成功的治疗效果是由于干扰α 4 β 1/VCAM-1介导的自身攻击性T细胞与血脑屏障的相互作用。尚未考虑α 4 β 7整合素的可能作用，或在EAE发病过程中干扰其他T细胞介导的事件。我们比较了单克隆抗体治疗对SJL/N小鼠EAE发展的影响，使用了大量针对α 4、β 7、α 4 β 7-异源二聚体和VCAM-1的单克隆抗体。虽然致脑炎性T细胞表达α 4-整联蛋白，但针对α 4 β 7-异源二聚体或β 7-亚基的mAb不干扰EAE的发展。相反，针对α 4和VCAM-1的mAb抑制或减少EAE的临床或组织病理学体征。我们的数据首次证明α 4 β 7对EAE的发展不是必需的。此外，我们的体外研究表明，抗α 4治疗EAE的治疗效果也可能是由抑制抗原特异性T细胞增殖引起的。
Because monoclonal antibodies (mAbs) directed against alpha 4-integrin and VCAM-1 inhibit the development of experimental autoimmune encephalomyelitis (EAE) in vivo, it has been concluded that the successful therapeutic effect is due to interference with alpha 4 beta 1/VCAM-1-mediated interaction of autoaggressive T cells with the blood-brain barrier. A possible role for alpha 4 beta 7-integrin, or interference with other T cell mediated events during the pathogenesis of EAE, has not been considered. We have compared the effects of mAb therapy on the development of EAE in the SJL/N mouse, using a large panel of mAbs directed against alpha 4, beta 7, the alpha 4 beta 7-heterodimer, and against VCAM-1. Although encephalitogenic T cells express both alpha 4-integrins, mAbs directed against the alpha 4 beta 7-heterodimer or against the beta 7-subunit did not interfere with the development of EAE. In contrast, mAbs directed against alpha 4 and VCAM-1 inhibited or diminished clinical or histopathological signs of EAE, Our data demonstrate for the first time that alpha 4 beta 7 is not essential for the development of EAE. Furthermore, our in vitro studies suggest that the therapeutic effect of anti-alpha 4-treatment of EAE might also be caused by inhibition of antigen-specific T cell proliferation.