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多发性硬化症患者中髓鞘碱性蛋白对CD4+和CD8+ T淋巴细胞的早期激活

Early activation of CD4+ and CD8+ T lymphocytes by myelin basic protein in subjects with MS.

作者信息

Arneth Borros

机构信息

Institute of Laboratory Medicine and Pathobiochemistry, Molecular Diagnostics, University Hospital of the Universities of Giessen and Marburg UKGM, Justus Liebig University Giessen, Feulgenstr. 12, 35392, Giessen, Germany.

出版信息

J Transl Med. 2015 Nov 2;13:341. doi: 10.1186/s12967-015-0715-6.

Abstract

BACKGROUND

Multiple sclerosis is the most common autoimmune disorder affecting the central nervous system. In this study, whole blood samples were analyzed for activation capacity and the activatability of CD4+ and CD8+ T-lymphocytes by human total myelin basic protein (MBP), human MBP 104-118 fragment, and guinea pig MBP 68-82 fragment.

METHODS

Whole blood samples from healthy human subjects were compared with samples from patients with multiple sclerosis (MS). In particular, the expression of CD69, a surface marker of T-lymphocyte activity, was measured via flow cytometry before and after 14 h of incubation with human total MBP, MBP 104-118 fragment and/or guinea pig MBP 68-82 fragment. The results were compared between 15 patients with MS and 15 healthy subjects.

RESULTS

In response to all three MBP forms, CD4+ and CD8+ T-lymphocytes from patients with MS demonstrated greater activatability than those from healthy subjects. These results indicate that in patients with MS, latent pre-activation to MBP epitopes results in an increased activation capacity of T-lymphocytes.

CONCLUSION

This effect may occur because immunization against MBP (at least in a subset of patients) plays a pathophysiological role in MS pathogenesis. Alternatively, this result may represent a non-specific, bystander autoimmune phenomenon.

摘要

背景

多发性硬化症是影响中枢神经系统的最常见自身免疫性疾病。在本研究中,对全血样本进行分析,以检测人总髓鞘碱性蛋白(MBP)、人MBP 104 - 118片段和豚鼠MBP 68 - 82片段对CD4 +和CD8 + T淋巴细胞的激活能力及可激活性。

方法

将健康人类受试者的全血样本与多发性硬化症(MS)患者的样本进行比较。具体而言,在与人总MBP、MBP 104 - 118片段和/或豚鼠MBP 68 - 82片段孵育14小时前后,通过流式细胞术测量T淋巴细胞活性的表面标志物CD69的表达。将15例MS患者和15名健康受试者的结果进行比较。

结果

针对所有三种MBP形式,MS患者的CD4 +和CD8 + T淋巴细胞表现出比健康受试者更高的可激活性。这些结果表明,在MS患者中,对MBP表位的潜在预激活导致T淋巴细胞激活能力增强。

结论

这种效应可能是因为针对MBP的免疫反应(至少在一部分患者中)在MS发病机制中发挥了病理生理作用。或者,这一结果可能代表一种非特异性的旁观者自身免疫现象。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/578e/4630877/7441d763082c/12967_2015_715_Fig1_HTML.jpg

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