INDUCTION OF PERSISTENTLY DEMYELINATED LESIONS IN THE RAT FOLLOWING THE REPEATED ADOPTIVE TRANSFER OF ENCEPHALITOGENIC T-CELLS AND DEMYELINATING ANTIBODY
INDUCTION OF PERSISTENTLY DEMYELINATED LESIONS IN THE RAT FOLLOWING THE REPEATED ADOPTIVE TRANSFER OF ENCEPHALITOGENIC T-CELLS AND DEMYELINATING ANTIBODY
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DOI：
10.1016/0165-5728(92)90136-9
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发表时间：
1992-10-01
影响因子：
3.3
通讯作者：
LASSMAN, H
中科院分区：
文献类型：
--
作者：
LININGTON, C;ENGELHARDT, B;LASSMAN, H
通过重复共转移致脑炎髓鞘碱性蛋白 (MBP) 特异性 T 细胞与髓鞘少突胶质细胞糖蛋白 (MOG) 特异性的脱髓鞘单克隆抗体 (mAb)，在 Lewis 大鼠中诱导出脱髓鞘实验性过敏性脑脊髓炎 (EAE) 慢性复发模型。在对照组中，每隔 18-21 天重复注射 5 X 10(5) MBP 特异性 T 细胞会导致对诱导 EAE 进一步发作的抵抗力增强。然而，每次 T 细胞移植后 4 天静脉注射 mAb 克服了这种“疫苗接种”效应，并诱导与不断增加和持续的神经功能缺损相关的严重临床复发。组织学检查显示，四个周期的 T 细胞和 mAb 治疗足以导致脊髓中形成大的脱髓鞘斑块，而这些斑块在最后一次注射 mAb 后 60 天内未能经历显着的髓鞘再生。这些病变由星形胶质细胞疤痕组织基质组成，其上有许多裸露的轴突。这些观察结果表明，Lewis 大鼠 T 细胞介导的 EAE 模型中大的、持续的脱髓鞘病变的形成取决于适当的抗髓磷脂自身抗体反应的存在。
A chronic relapsing model of demyelinating experimental allergic encephalomyelitis (EAE) was induced in Lewis rats by the repeated co-transfer of encephalitogenic, myelin basic protein (MBP)-specific T cells in combination with a demyelinating monoclonal antibody (mAb) specific for the myelin oligodendrocyte glycoprotein (MOG). In controls, repeated injections of 5 X 10(5) MBP-specific T cells at intervals of 18-21 days resulted in an increasing resistance to the induction of further episodes of EAE. However, intravenous injection of the mAb 4 days after each T cell transfer overcame this 'vaccination' effect and induced severe clinical relapses associated with an increasing and persistent neurological deficit. Histological examination revealed that four cycles of treatment with T cells and mAb were sufficient to result in the formation of large plaques of demyelination in the spinal cord that failed to undergo significant remyelination within 60 days of the final injection of mAb. These lesions consisted of a matrix of astrocytic scar tissue traversed by numerous naked axons. These observations demonstrate that the formation of large, persistently, demyelinated lesions in a T cell-mediated model of EAE in the Lewis rat is dependent on the presence of an appropriate anti-myelin autoantibody response.