Engelhardt B, Laschinger M, Schulz M, Samulowitz U, Vestweber D, Hoch G
Max-Planck Institut für physiologische und klinische Forschung, W.G. Kerckhoff-Institut, Bad Nauheim, Germany.
J Clin Invest. 1998 Dec 15;102(12):2096-105. doi: 10.1172/JCI4271.
Because monoclonal antibodies (mAbs) directed against alpha4-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 alpha4beta1/VCAM-1-mediated interaction of autoaggressive T cells with the blood-brain barrier. A possible role for alpha4beta7-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 alpha4, beta7, the alpha4beta7-heterodimer, and against VCAM-1. Although encephalitogenic T cells express both alpha4-integrins, mAbs directed against the alpha4beta7-heterodimer or against the beta7-subunit did not interfere with the development of EAE. In contrast, mAbs directed against alpha4 and VCAM-1 inhibited or diminished clinical or histopathological signs of EAE. Our data demonstrate for the first time that alpha4beta7 is not essential for the development of EAE. Furthermore, our in vitro studies suggest that the therapeutic effect of anti-alpha4-treatment of EAE might also be caused by inhibition of antigen-specific T cell proliferation.
由于针对α4整合素和血管细胞黏附分子-1（VCAM-1）的单克隆抗体（mAb）在体内可抑制实验性自身免疫性脑脊髓炎（EAE）的发展，因此得出结论，成功的治疗效果是由于干扰了α4β1/VCAM-1介导的自身攻击性T细胞与血脑屏障的相互作用。α4β7整合素的可能作用，或在EAE发病机制中对其他T细胞介导事件的干扰，尚未得到考虑。我们使用大量针对α4、β7、α4β7异二聚体和VCAM-1的单克隆抗体，比较了单克隆抗体治疗对SJL/N小鼠EAE发展的影响。尽管致脑炎T细胞同时表达α4整合素，但针对α4β7异二聚体或β7亚基的单克隆抗体并未干扰EAE的发展。相反，针对α4和VCAM-1的单克隆抗体抑制或减轻了EAE的临床或组织病理学症状。我们的数据首次证明α4β7对EAE的发展并非必不可少。此外，我们的体外研究表明，抗α4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。
