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重症肌无力中异常的T细胞受体V基因使用情况:扩增的T细胞群体的患病率及特征

Abnormal T cell receptor V gene usage in myasthenia gravis: prevalence and characterization of expanded T cell populations.

作者信息

Xu B Y, Giscombe R, Söderlund A, Troye-Blomberg M, Pirskanen R, Lefvert A K

机构信息

Immunological Research Unit, Centre for Molecular Medicine, Karolinska Hospital, Stockholm, Sweden.

出版信息

Clin Exp Immunol. 1998 Sep;113(3):456-64. doi: 10.1046/j.1365-2249.1998.00675.x.

DOI:10.1046/j.1365-2249.1998.00675.x
PMID:9737677
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1905055/
Abstract

The usage of T cell receptor (TCR) Valpha/Vbeta chains on cells from 38 patients with myasthenia gravis (MG) was determined by flow cytometry. There was a decreased number of cells expressing Vbeta2 in CD8+ and Vbeta3 in CD4+ cells in patients compared with healthy individuals. Abnormal expansions of T cells using particular TCR Valpha/Vbeta gene products were found in 18/38 patients. A significantly higher usage of Vbeta13 was observed but there was no restriction with regard to other TCR Valpha/Vbeta. Expanded cells belonging to both CD4+ and CD8+ were present in MG patients while restricted to the CD8+ population in healthy individuals. To elucidate the role of the expanded populations, we studied characteristics of the expanded and non-expanded T cells from MG patients who had persistent T cell expansions over more than 2 years. The cells were analysed with regard to phenotype, cytokine secretion, cytokine mRNA expression and reactivity with the autoantigen, the acetylcholine receptor. The characteristics of the expanded populations in MG clearly differed from those found in healthy individuals. More cells in the CD4+ expanded populations expressed HLA-DR and there was also a tendency for higher expression of CD25, CD28 and CD57. The number of cells spontaneously secreting cytokines was higher in the expanded populations. A dominant Th1-type cytokine secretion and mRNA expression was noted. Autoantigen-reactive CD4+ T cells were largely restricted to the expanded populations.

摘要

采用流式细胞术检测了38例重症肌无力(MG)患者细胞上T细胞受体(TCR)Vα/Vβ链的使用情况。与健康个体相比,患者CD8⁺细胞中表达Vβ2的细胞数量减少,CD4⁺细胞中表达Vβ3的细胞数量减少。在38例患者中有18例发现使用特定TCR Vα/Vβ基因产物的T细胞异常扩增。观察到Vβ13的使用显著增加,但对其他TCR Vα/Vβ没有限制。MG患者中同时存在属于CD4⁺和CD8⁺的扩增细胞,而健康个体中仅局限于CD8⁺群体。为了阐明扩增群体的作用,我们研究了MG患者中持续T细胞扩增超过2年的扩增和未扩增T细胞的特征。对细胞进行了表型、细胞因子分泌、细胞因子mRNA表达以及与自身抗原乙酰胆碱受体反应性的分析。MG中扩增群体的特征明显不同于健康个体中发现的特征。CD4⁺扩增群体中有更多细胞表达HLA-DR,CD25、CD28和CD57的表达也有升高趋势。扩增群体中自发分泌细胞因子的细胞数量更多。观察到主要为Th1型细胞因子分泌和mRNA表达。自身抗原反应性CD4⁺ T细胞主要局限于扩增群体。

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