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视神经炎和多发性硬化症中的自身免疫性T细胞库:识别多种髓鞘蛋白的T细胞在脑脊液中积聚。

Autoimmune T cell repertoire in optic neuritis and multiple sclerosis: T cells recognising multiple myelin proteins are accumulated in cerebrospinal fluid.

作者信息

Söderström M, Link H, Sun J B, Fredrikson S, Wang Z Y, Huang W X

机构信息

Department of Neurology, Karolinska Institutet, Huddinge Hospital, Stockholm, Sweden.

出版信息

J Neurol Neurosurg Psychiatry. 1994 May;57(5):544-51. doi: 10.1136/jnnp.57.5.544.

Abstract

Monosymptomatic unilateral optic neuritis is a common first manifestation of multiple sclerosis. Abnormal T cell responses to myelin components including myelin basic protein (MBP), proteolipid protein (PLP), and myelin-associated glycoprotein (MAG) have been implicated in the pathogenesis of multiple sclerosis. Antigen-reactive T helper type 1 (Th1)-like cells that responded by interferon gamma (IFN-gamma) secretion on antigen stimulation in vitro were counted. Untreated patients with optic neuritis and multiple sclerosis had similarly raised levels of T cells recognising MBP, PLP, and MAG in peripheral blood. Such T cells were strongly enriched in CSF. None of these myelin antigens functioned as immunodominant T cell antigen characteristic for optic neuritis or multiple sclerosis. The autoimmune T cell repertoire was not more restricted in optic neuritis (as an example of early multiple sclerosis). The autoreactive T cell repertoires differed in blood compared with CSF in individual patients with optic neuritis and multiple sclerosis. No relations were found between specificity or quantity of autoreactive T cells in blood or CSF, and clinical variables of optic neuritis or multiple sclerosis, or occurrence of oligoclonal IgG bands in CSF. The role of raised MBP, PLP, and MAG reactive Th1-like cells found in optic neuritis and multiple sclerosis remains unexplained.

摘要

单症状性单侧视神经炎是多发性硬化症常见的首发表现。对包括髓鞘碱性蛋白(MBP)、蛋白脂蛋白(PLP)和髓鞘相关糖蛋白(MAG)在内的髓鞘成分的异常T细胞反应与多发性硬化症的发病机制有关。对体外抗原刺激时通过分泌γ干扰素(IFN-γ)做出反应的抗原反应性1型辅助性T(Th1)样细胞进行计数。未经治疗的视神经炎和多发性硬化症患者外周血中识别MBP、PLP和MAG的T细胞水平同样升高。此类T细胞在脑脊液中显著富集。这些髓鞘抗原均未作为视神经炎或多发性硬化症特有的免疫显性T细胞抗原发挥作用。自身免疫性T细胞库在视神经炎(作为早期多发性硬化症的一个例子)中并未受到更多限制。在患有视神经炎和多发性硬化症的个体患者中,血液中的自身反应性T细胞库与脑脊液中的不同。在血液或脑脊液中自身反应性T细胞的特异性或数量与视神经炎或多发性硬化症的临床变量,或脑脊液中寡克隆IgG带的出现之间未发现相关性。在视神经炎和多发性硬化症中发现的MBP、PLP和MAG反应性Th1样细胞水平升高的作用仍未得到解释。

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