Oligoclonality of CD8+ T cells in multiple sclerosis

Oligoclonality of CD8+ T cells in multiple sclerosis
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DOI:
10.3109/08916939608995336
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发表时间:
1996-01-01
期刊:
影响因子:
3.5
通讯作者:
Gregersen, PK
Gregersen, PK
中科院分区:
医学4区
文献类型:
--
作者:
Monteiro, J;Hingorani, R;Gregersen, PK

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我们之前已经表明,CD8+ T细胞低克隆性在正常人中经常发生,并且通常表现出非常多样化的曲目。为了研究CD8+ T细胞在MS中的作用,我们分析了125名处于不同疾病阶段的MS患者的CD8低克隆性。采用CDR3长度变异多重PCR检测25个TCRBV片段/家族的低克隆性。与正常对照比较,MS患者的CD8 T细胞库显示TCRBV9、-18和-23家族的低克隆性频率增加,对这些克隆优势CD8+细胞的TCRs序列分析显示,总体上具有高度的多样性,然而,我们在两个无关的MS患者的CD8细胞中观察到一个相同的TCRBV18序列。在EAE和MS中发现了与MS脑和MBP特异性T细胞克隆同源的几个TCRs,未来对这些克隆扩增群体的功能和特异性的表征可能有助于深入了解这种自身免疫性疾病中免疫失调的本质。
We have shown earlier that CD8+ T cell oligoclonality occurs frequently in normal individuals and generally exhibits a very diverse repertoire, In order to investigate the role of CD8+ T cells in MS, we analysed CD8 olgoclonality in 125 patients with MS in varying stages of disease. A multiplex PCR assay for CDR3 length variation was employed to detect oligoclonality in 25 TCRBV segments/families. CD8 clonal dominance was found to be frequent in MS, Comparison of the CD8 T cell repertoire in MS with that in normal controls revealed an increased frequency of oligoclonality involving the TCRBV9, -18 and -23 families, Sequence analysis of the TCRs from these clonally dominant CD8+ cells revealed a high degree of diversity overall, However, we observed one instance of identical TCRBV18 sequences in CD8 cells from two unrelated MS patients, In addition, several TCRs with motifs homologous to those found in MS brain and MBP specific T cell clones in EAE and MS were also detected, Future characterization of the function and specificity of these clonally expanded populations may provide insight into the nature of immune dysregulation in this autoimmune disorder.