Regional variation of the αβ T cell repertoire in the colon of healthy individuals and patients with Crohn's disease
Regional variation of the αβ T cell repertoire in the colon of healthy individuals and patients with Crohn's disease
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DOI：
10.1016/s0198-8859(02)00378-6
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发表时间：
2002-06-01
期刊：
影响因子：
2.7
通讯作者：
Duchmann, R
中科院分区：
文献类型：
--
作者：
May, E;Lambert, C;Duchmann, R
克隆扩增的 T 细胞可能参与克罗恩病 (CD) 的发病机制。为了测试 CD 对扩增 T 细胞区域分布的影响，本研究通过 TCR 谱分型分析了 12 名 CD 患者和 6 名非炎症对照者的结肠活检标本中的 T 细胞受体 β (TCRB) 库。来自正常粘膜不同部位的显性 CDR3 带的迁移特征表明单个扩增克隆的局灶性、节段性或普遍性扩散。当比较 CD 患者结肠的炎症和非炎症区域时，观察到类似的模式，这表明 T 细胞的区域扩张与解剖学邻近性的关系比与局部炎症活动的关系更密切。在 3 名 CD 患者发炎结肠中选择性扩增的 TCRBV12+ T 细胞的 CDR3 序列分析未能揭示公共 CDR3 基序。我们的数据表明，正常肠粘膜中存在不同的区域 T 细胞扩增模式，这种模式不会受到慢性肠道炎症的显着破坏。这并不排除CD中扩增的T细胞通过更微妙的变化发挥致病作用，但强调需要将它们与正常结肠中克隆扩增的T细胞的不连续分布区分开来。
Clonally expanded T cells might be involved in the pathogenesis of Crohn's disease (CD). To test the impact of CD on the regional distribution of expanded T cells, this study analyzed the T cell receptor beta (TCRB) repertoire within colonic biopsy specimens from 12 CD patients and 6 noninflammatory controls by TCR spectra-typing. Migration characteristics of dominant CDR3 bands from different sites of the normal mucosa suggested focal, segmental, or ubiquitous spreading of individual expanded clones. Similar patterns were observed when inflamed and noninflamed areas of the colon of CD patients were compared, suggesting that regional expansion of T cells was more closely related to anatomic proximity than to local inflammatory activity. CDR3-sequence analysis of TCRBV12+ T cells, which were selectively expanded in the inflamed colon of 3 CD patients, failed to reveal a public CDR3 motif. Our data indicate the existence of distinct patterns of regional T cell expansions in the normal gut mucosa, which are not significantly disrupted by chronic intestinal inflammation. This does not exclude a pathogenic role of expanded T cells in CD through more subtle changes, but emphasizes the need to distinguish them from a discontinuous distribution of clonally expanded T cells in normal colon.