An antibody to lymphotoxin and tumor necrosis factor prevents transfer of experimental allergic encephalomyelitis.
An antibody to lymphotoxin and tumor necrosis factor prevents transfer of experimental allergic encephalomyelitis.
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DOI：
10.1084/jem.172.4.1193
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发表时间：
1990-10-01
期刊：
影响因子：
--
通讯作者：
Clark RB
中科院分区：
文献类型：
--
作者：
Ruddle NH;Bergman CM;McGrath KM;Lingenheld EG;Grunnet ML;Padula SJ;Clark RB
关于致病机制的不确定性一直是有效预防和治疗人类神经系统疾病如多发性硬化症、热带痉挛性下肢轻瘫和艾滋病脱髓鞘疾病的主要障碍。在此，我们将肿瘤坏死因子β（LT）和TNF-α与实验性过敏性脑脊髓炎（EAE）（一种自身免疫性脱髓鞘疾病的小鼠模型）联系起来。在这篇文章中，我们报告了用中和LT和TNF-α的抗体治疗受体小鼠可以防止克隆介导的EAE的转移。LNC-8是一种髓鞘碱性蛋白特异性T细胞系，在被伴刀豆球蛋白A（T细胞受体CD-3 ε组分的抗体）或在同基因脾细胞中呈现的髓鞘碱性蛋白激活后产生高水平的LT和TNF-α。LNC-8细胞转移EAE的临床体征。当LNC-8受体小鼠也用TN3.19.12（一种中和LT和TNF-α的单克隆抗体）治疗时，转移的EAE的严重程度降低，而对照抗体没有改变疾病。抗LT/TNF-α治疗的效果是长期的，并已持续5个月。这些发现表明LT和TNF-α以及产生它们的T细胞在EAE中起重要作用。
Uncertainty regarding pathogenic mechanisms has been a major impediment to effective prevention and treatment for human neurologic diseases such as multiple sclerosis, tropical spastic paraparesis, and AIDS demyelinating disease. Here, we implicate lymphotoxin (LT) (tumor necrosis factor beta [TNF-beta]) and TNF-alpha in experimental allergic encephalomyelitis (EAE), a murine model of an autoimmune demyelinating disease. In this communication, we report that treatment of recipient mice with an antibody that neutralizes LT and TNF-alpha prevents transfer of clone-mediated EAE. LNC-8, a myelin basic protein-specific T cell line, produces high levels of LT and TNF-alpha after activation by concanavalin A, antibody to the CD-3 epsilon component of the T cell receptor, or myelin basic protein presented in the context of syngeneic spleen cells. LNC-8 cells transfer clinical signs of EAE. When LNC-8 recipient mice were also treated with TN3.19.12, a monoclonal antibody that neutralizes LT and TNF-alpha, the severity of the transferred EAE was reduced, while control antibodies did not alter the disease. The effect of anti-LT/TNF-alpha treatment was long lived and has been sustained for 5 mo. These findings suggest that LT and TNF-alpha and the T cells that produce them play an important role in EAE.