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视神经炎与多发性硬化症:针对髓鞘蛋白和髓磷脂碱性蛋白肽段的T细胞受体库随时间变化。

Optic neuritis and multiple sclerosis: the T cell repertoires to myelin proteins and MBP peptides change with time.

作者信息

Söderström M, Link H, Fredrikson S, Sun J B

机构信息

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

出版信息

Acta Neurol Scand. 1994 Jul;90(1):10-8. doi: 10.1111/j.1600-0404.1994.tb02673.x.

Abstract

Autoreactive T cells recognizing myelin basic protein (MBP), proteolipid protein (PLP) and MBP peptides have been described in multiple sclerosis (MS) and optic neuritis (ON), but their role in disease pathogenesis, if any, is unknown. A consistency of the T cell repertoire over the course of MS and ON should facilitate the development of specific immunotherapies. We have examined the T cell responses to autoantigens in two consecutive blood specimens taken from patients with ON and MS, and in two consecutive CSF specimens obtained from ON patients. As read-out numbers of T cells responding to antigen stimulation by the secretion of interferon-gamma were estimated. Pronounced differences in occurrence and numbers of T cells recognizing MBP, MBP peptides with the amino acid sequences 63-88, 110-128 and 148-165, and PLP were noticed in individual ON and MS patients over the course of disease. The MBP peptide among those three included, that was predominantly recognized by T cells in the individual patient, also varied over the course. The quantitative and qualitative changes of the myelin antigen-specific T cell response in MS and in ON, the latter to a certain extent reflecting the situation in early MS, do not favor the future useful development of specific immunotherapies in these diseases.

摘要

在多发性硬化症(MS)和视神经炎(ON)中,已发现可识别髓鞘碱性蛋白(MBP)、蛋白脂蛋白(PLP)和MBP肽段的自身反应性T细胞,但它们在疾病发病机制中的作用(如果有)尚不清楚。MS和ON病程中T细胞库的一致性应有助于特异性免疫疗法的开发。我们检测了从ON和MS患者采集的两份连续血液标本以及从ON患者获得的两份连续脑脊液标本中T细胞对自身抗原的反应。通过γ干扰素分泌情况估计对抗原刺激作出反应的T细胞数量。在疾病过程中,个体ON和MS患者中识别MBP、氨基酸序列为63 - 88、110 - 128和148 - 165的MBP肽段以及PLP的T细胞在出现频率和数量上存在明显差异。在这三个包含的MBP肽段中,个体患者中主要被T细胞识别的肽段在病程中也有所不同。MS和ON中髓鞘抗原特异性T细胞反应的定量和定性变化,后者在一定程度上反映了早期MS的情况,不利于这些疾病未来特异性免疫疗法的有效开发。

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