CD8+ T cells were sorted from colon biopsy specimens and blood for T-cell receptor (TCR) β-chain sequencing. Biopsy specimens from inflamed or uninflamed colon from ulcerative colitis or Crohn\'s disease cohorts were compared with colon biopsy specimens from people without IBD, as well as with autologous blood α4β7+, α4β7- effector/memory, terminal effector/memory CD45RA+ T cell, and mucosal-associated invariant T-cell CD8 subpopulations.
CD8 TCR diversity in mucosa and blood did not correlate with inflammation. Repertoire overlap between any 2 distinct locations of a given person\'s colon was consistently high, although often lower between inflamed and uninflamed sites. CD8 TCR repertoires overlapped between the colon and each peripheral blood subpopulation studied, with the highest overlap seen for integrin α4β7+ T cells. Inflamed tissue consistently overlapped more than uninflamed tissue with each blood subpopulation.
CD8 T-cell clones are spread homogenously throughout the length of the colon. Although TCR repertoire overlap is greater within than between inflamed and uninflamed colon segments, a similar TCR diversity in both argues against local clonal expansion being the main source of excess cytotoxic T cells in inflamed mucosa. Rather, the increased TCR overlap observed between blood and inflamed mucosa supports the significance of T-cell trafficking in IBD pathogenesis, particularly concerning α4β7+ T-cell populations.
方法:从结肠活检和血液中分选CD8+T细胞进行T细胞受体(TCR)-β链测序。来自溃疡性结肠炎或克罗恩病的发炎或未发炎结肠的活检与来自非IBD患者的结肠活检进行比较。以及自体血α4β7+,α4β7-效应子/记忆,TEMRA,和MAITCD8亚群。
结果:粘膜和血液中的CD8TCR多样性与炎症无关。给定人结肠的任何两个不同位置之间的重复重叠始终很高,虽然通常在发炎和未发炎的部位之间较低。研究的结肠和每个外周血亚群之间的CD8TCR谱重叠,对于整合素α4β7+T细胞观察到最高重叠。与每个血液亚群相比,发炎的组织始终重叠多于未发炎的组织。
结论:CD8T细胞克隆均匀地散布在整个结肠长度上。尽管TCR库重叠在发炎和未发炎的结肠段之间更大,两者中TCR的相似多样性表明,局部克隆扩增是发炎粘膜中过多的细胞毒性T细胞的主要来源。相反,血液和发炎粘膜之间观察到的TCR重叠增加支持T细胞运输在IBD发病机制中的意义,特别是关于α4β7+T细胞群体。