Holmén Nathalie, Lundgren Anna, Lundin Samuel, Bergin Ann-Marie, Rudin Anna, Sjövall Henrik, Ohman Lena
Department of Internal Medicine, Sahlgrenka Academy, Göteborg University, Göteborg, Sweden.
Inflamm Bowel Dis. 2006 Jun;12(6):447-56. doi: 10.1097/00054725-200606000-00003.
Factors determining the extension and degree of inflammation in the colonic mucosa of patients with ulcerative colitis (UC) are largely unknown, but CD4+CD25high regulatory T cells (Tregs) have been implicated to play an important role in suppressing inflammation. Therefore, the aims of this study were to determine whether colonic Tregs have suppressive effects on colonic effector T cells in UC and to analyze the association between segmental colonic Treg distribution and disease activity.
The suppressive activity of colonic CD4+CD25high Tregs from patients with active UC was determined in coculture assays measuring proliferation and cytokine production. The frequency of Tregs and the expression of the Treg marker FOXP3 were analyzed with flow cytometry and RT-PCR in isolated cells and the whole mucosa from patients with active and inactive disease, as well as healthy mucosa.
Colonic CD4+CD25high T cells from patients with UC suppressed the proliferation and cytokine secretion of colonic effector CD4+ T cells. Healthy controls but not patients with UC had lower Treg frequencies in the sigmoid than in the ascending colon. Patients with UC with active disease had increased frequency of colonic Tregs. The frequency of Tregs was positively correlated with colonic disease activity and serum C-reactive protein.
Colonic CD4+CD25high Tregs are able to suppress colonic effector T cell activity in vitro, and the Treg frequency in the inflamed intestine increases with disease activity in patients with active UC. This suggests that Tregs may be outnumbered by other inflammatory cells or that their suppressive activity may be influenced by the in vivo environment.
溃疡性结肠炎（UC）患者结肠黏膜炎症的扩展范围和程度的决定因素尚不清楚，但CD4 + CD25高调节性T细胞（Tregs）被认为在抑制炎症中起重要作用。因此，本研究的目的是确定结肠Tregs对UC患者结肠效应T细胞是否具有抑制作用，并分析节段性结肠Treg分布与疾病活动之间的关联。
在测量增殖和细胞因子产生的共培养试验中，测定活动期UC患者结肠CD4 + CD25高Tregs的抑制活性。采用流式细胞术和RT-PCR分析活动期和非活动期疾病患者以及健康黏膜的分离细胞和全黏膜中Tregs的频率和Treg标志物FOXP3的表达。
UC患者的结肠CD4 + CD25高T细胞抑制结肠效应CD4 + T细胞的增殖和细胞因子分泌。健康对照者而非UC患者乙状结肠中的Treg频率低于升结肠。活动期疾病的UC患者结肠Tregs频率增加。Tregs频率与结肠疾病活动度和血清C反应蛋白呈正相关。
结肠CD4 + CD25高Tregs在体外能够抑制结肠效应T细胞活性，并且活动期UC患者炎症肠段中的Treg频率随疾病活动度增加。这表明Tregs可能在数量上少于其他炎性细胞，或者其抑制活性可能受体内环境影响。
