Data from: Human blood and mucosal regulatory T cells express activation markers and inhibitory receptors in inflammatory bowel disease

Background: FOXP3+ regulatory T cells (Tregs) are critical for preventing intestinal inflammation. However, FOXP3+ T cells are paradoxically increased in the intestines of patients with the inflammatory bowel disease (IBD) ulcerative colitis (UC) or Crohn's disease (CD). We determined whether these FOXP3+ cells in IBD patients share or lack the phenotype of such cells from patients without IBD. Methods: We quantified and characterized FOXP3+ Treg populations, as well as FOXP3- CD4+ T cells, in the lamina propria lymphocytes (LPL) of intestine surgically resected from patients with and without IBD, and in the blood of controls or Crohn's patients with or without disease activity. Results: In all samples, a similar fraction of FOXP3+ cells expressed the "natural" Treg (nTreg) marker Helios, suggesting that, in IBD, these cells are not entirely "induced" Tregs (iTregs) derived from activated effector T cells. Helios+ and Helios- FOXP3+ T cells demonstrated similar expression of maturation markers, activation markers, and inhibitory molecules between IBD patients and controls, while FOXP3- cells paradoxically expressed more of the inhibitory receptors CD39, CTLA4, and PD-1 in inflamed mucosa. Greater expression of activation markers was also seen in both Helios+ and Helios- Tregs, relative to FOXP3- cells, in both IBD patients and controls, indicating that Tregs are effectively activated by antigen in IBD. Conclusions: Extensive immunophenotyping revealed that Helios+ and Helios- mucosal Tregs exist at a similar frequency, and have a similar expression of inhibitory molecules and activation markers in patients with IBD as in healthy controls.

背景：FOXP3+调节性T细胞（FOXP3+ regulatory T cells, Tregs）对预防肠道炎症至关重要。然而，炎症性肠病（inflammatory bowel disease, IBD）、溃疡性结肠炎（ulcerative colitis, UC）或克罗恩病（Crohn's disease, CD）患者肠道内的FOXP3+ T细胞却反常增多。本研究旨在明确IBD患者体内的此类FOXP3+细胞，与非IBD患者体内的同类细胞，是否共享或缺失相应的表型特征。方法：我们对IBD患者与非IBD患者手术切除的肠道固有层淋巴细胞（lamina propria lymphocytes, LPL），以及健康对照者或伴/不伴疾病活动度的克罗恩病患者的血液样本，开展了FOXP3+ Treg群体的定量分析与表型鉴定，同时也对FOXP3阴性CD4+ T细胞进行了检测。结果：所有样本中，相似比例的FOXP3+细胞表达"天然"Treg（natural Treg, nTreg）标志物Helios，这提示在IBD患者体内，此类细胞并非完全源自活化效应T细胞的"诱导性"Treg（induced Treg, iTregs）。与健康对照相比，IBD患者体内Helios阳性与Helios阴性的FOXP3+ T细胞在成熟标志物、活化标志物及抑制性分子的表达上均无显著差异；而FOXP3阴性细胞则在炎症黏膜中反常高表达抑制性受体CD39、CTLA4及PD-1。相较于FOXP3阴性细胞，无论IBD患者还是健康对照，Helios阳性与Helios阴性的Treg的活化标志物表达水平均更高，这表明IBD患者体内的Treg可被抗原有效活化。结论：全面的免疫表型分析显示，在IBD患者与健康对照中，Helios阳性与Helios阴性的黏膜Treg的分布频率相似，且抑制性分子与活化标志物的表达模式亦无显著差异。