T-CELLS SPECIFIC FOR THE MYELIN OLIGODENDROCYTE GLYCOPROTEIN MEDIATE AN UNUSUAL AUTOIMMUNE INFLAMMATORY RESPONSE IN THE CENTRAL-NERVOUS-SYSTEM
T-CELLS SPECIFIC FOR THE MYELIN OLIGODENDROCYTE GLYCOPROTEIN MEDIATE AN UNUSUAL AUTOIMMUNE INFLAMMATORY RESPONSE IN THE CENTRAL-NERVOUS-SYSTEM
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DOI：
10.1002/eji.1830230627
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发表时间：
1993-06-01
影响因子：
5.4
通讯作者：
WEKERLE, H
中科院分区：
文献类型：
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作者：
LININGTON, C;BERGER, T;WEKERLE, H
髓鞘少突胶质细胞糖蛋白（MOG）特异性T细胞介导中枢神经系统（CNS）中的自身免疫炎症反应，其与T细胞介导的实验性过敏性脑脊髓炎（EAE）的常规模型完全不同。使用合成肽，在蛋白质的胞外IgG V样结构域氨基酸44-53（FSRVVHLYRN）内鉴定了刘易斯大鼠的MOG的致脑炎性T细胞表位。然而，与髓鞘碱性蛋白（MBP）特异性T细胞系诱导的炎症反应不同，MOG肽特异性T细胞介导的炎症未能诱导总体神经功能缺损。（与血管周围相反）炎症，选择性减少浸润CNS的ED 1+巨噬细胞的数量，以及完全缺乏外周神经炎症。巨噬细胞向CNS的募集减少不能归因于T细胞系合成干扰素-γ、肿瘤坏死因子-α、白细胞介素（IL）-6或IL-2的缺陷。此外，这种亚临床炎症反应诱导严重的血脑屏障功能障碍，如通过静脉注射脱髓鞘MOG特异性单克隆抗体后诱导严重的临床疾病所证明的。因此，EAE中的神经功能缺损表现出对靶自身抗原的身份的意外依赖性，其决定了局部炎症反应的程度和性质，并最终决定了神经功能缺损的程度。
Myelin oligodendrocyte glycoprotein (MOG)-specific T cells mediate an autoimmune inflammatory response in the central nervous system (CNS) that differs radically from conventional models of T cell-mediated experimental allergic encephalomyelitis (EAE). Using synthetic peptides an encephalitogenic T cell epitope of MOG for the Lewis rat was identified within the extracellular IgG V-like domain of the protein, amino acids 44-53 (FSRVVHLYRN).The adoptive transfer of CD4+ T cells specific for this epitope induce an intense, dose-dependent inflammatory response in the CNS of naive syngeneic recipients. However, unlike the inflammatory response induced by myelin basic protein (MBP)-specific T cell lines, inflammation mediated by the MOG peptide-specific T cells failed to induce a gross neurological deficit.This unexpected observation was not due to a reduction in the overall inflammatory response in the CNS, but was specifically associated with a decrease in the extent of parenchymal (as opposed to perivascular) inflammation, a selective decrease in the number of ED1+ macrophages infiltrating the CNS, and a total lack of peripheral nerve inflammation. The decreased recruitment of macrophages into the CNS could not be ascribed to deficiences in the synthesis of interferon-gamma, tumor necrosis factor-a, interleukin (IL)-6 or IL-2 by the T cell line. Moreover, this sub-clinical inflammatory response induced severe blood-brain barrier dysfunction as demonstrated by the induction of severe clinical disease following intravenous injection of a demyelinating MOG-specific monoclonal antibody. The neurological deficit in EAE thus exhibits an unexpected dependence on the identity of the target autoantigen, which determines the extent and nature of the local inflammatory response and ultimately the extent of the neurological deficit.