Clonal expansions of CD8(+) T cells dominate the T cell infiltrate in active multiple sclerosis lesions as shown by micromanipulation and single cell polymerase chain reaction.
Clonal expansions of CD8(+) T cells dominate the T cell infiltrate in active multiple sclerosis lesions as shown by micromanipulation and single cell polymerase chain reaction.
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DOI：
10.1084/jem.192.3.393
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发表时间：
2000-08-07
期刊：
影响因子：
--
通讯作者：
Rajewsky K
中科院分区：
文献类型：
--
作者：
Babbe H;Roers A;Waisman A;Lassmann H;Goebels N;Hohlfeld R;Friese M;Schröder R;Deckert M;Schmidt S;Ravid R;Rajewsky K
在单细胞水平上以前所未有的分辨率确定了浸润活动性脱髓鞘多发性硬化症 (MS) 病变的 CD4+ 和 CD8+ T 细胞的克隆组成和 T 细胞受体 (TCR) 库。通过显微操作从病变组织的冷冻切片中分离出单个 CD4+ 或 CD8+ T 细胞，并进行 TCR-β 基因重排的单靶扩增。该策略允许将 TCR 可变区（V 区）序列分配给扩增该序列的特定 T 细胞。序列分析显示，在所研究的两个案例中，大多数 CD8+ T 细胞属于少数克隆。在案例 1 中，这些克隆之一占 CD8+ T 细胞的 35%。V 区序列比较揭示了案例 1 中一些 CD8+ T 细胞的共同肽特异性选择的迹象。在这两种情况下，CD4+ T 细胞群都更加异质。大多数 CD4+ 和 CD8+ 克隆出现在血管周围浸润以及实质 T 细胞中。在病例2中，在脑组织中发现的两个CD8+克隆也在外周血中检测到。研究扩增克隆的抗原特异性可能有助于阐明其功能特性。
Clonal composition and T cell receptor (TCR) repertoire of CD4+ and CD8+ T cells infiltrating actively demyelinating multiple sclerosis (MS) lesions were determined with unprecedented resolution at the level of single cells. Individual CD4+ or CD8+ T cells were isolated from frozen sections of lesional tissue by micromanipulation and subjected to single target amplification of TCR-β gene rearrangements. This strategy allows the assignment of a TCR variable region (V region) sequence to the particular T cell from which it was amplified. Sequence analysis revealed that in both cases investigated, the majority of CD8+ T cells belonged to few clones. One of these clones accounted for 35% of CD8+ T cells in case 1. V region sequence comparison revealed signs of selection for common peptide specificities for some of the CD8+ T cells in case 1. In both cases, the CD4+ T cell population was more heterogeneous. Most CD4+ and CD8+ clones were represented in perivascular infiltrates as well as among parenchymal T cells. In case 2, two of the CD8+ clones identified in brain tissue were also detected in peripheral blood. Investigation of the antigenic specificities of expanded clones may help to elucidate their functional properties.
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影响因子：
11.2
作者：
BRUCK, W;SCHMIED, M;LASSMANN, H
通讯作者：
LASSMANN, H
影响因子：
3.3
作者：
CHOU, YK;BOURDETTE, DN;VANDENBARK, AA
通讯作者：
VANDENBARK, AA
影响因子：
15.3
作者：
HAFLER, DA;DUBY, AD;WEINER, HL
通讯作者：
WEINER, HL
影响因子：
--
作者：
Delfino, L;Morabito, A;Ferrara, GB
通讯作者：
Ferrara, GB
影响因子：
11.2
作者：
BRUCK, W;PORADA, P;LASSMANN, H
通讯作者：
LASSMANN, H