Laboratory of Experimental Immunology, Catholic University of Leuven, Leuven, Belgium.
Inflamm Bowel Dis. 2010 Aug;16(8):1299-310. doi: 10.1002/ibd.21229.
Immune therapies may act in inflammatory bowel diseases (IBD) by modulating regulatory T cells (Tregs). Therefore, we investigated the effect of infliximab (IFX) therapy on Forkhead box protein3 (Foxp3) T cells in blood and intestinal mucosa from Crohn's disease (CD) and ulcerative colitis (UC).
Forty patients with active IBD (23 CD / 17 UC) were treated with IFX 5 mg/kg intravenously at weeks 0, 2, 6, and each 8 weeks thereafter. Blood samples were obtained before every infusion and T-lymphocyte subsets were characterized by flow cytometry. Foxp3 expression in intestinal biopsies from 43 patients with active IBD (19 CD / 24 UC) before and after IFX infusion and from 6 controls were assessed by quantitative reverse-transcription polymerase chain reaction and immunohistochemistry. Plasma C-reactive protein (CRP), clinical response, and endoscopic healing data were collected in parallel.
IFX therapy resulted in a significant and sustained relative increase of CD4(+)CD25(+)Foxp3(+) Treg and of CD4(+)CD25(-)Foxp3(+) Treg cells in peripheral blood (both P < 0.0001 compared to baseline), particularly in responders (both P < 0.05 compared to nonresponders). The change in CRP over time inversely correlated with the increase of CD25(+)Foxp3(+) cells (P < 0.001, r = -0.39) and durable clinical response was associated with a sustained increase of circulating Foxp3(+) cells. Surprisingly, IFX therapy downregulated mucosal mRNA and protein expression of Foxp3 in UC and CD responders (both P < 0.001) but not in nonresponders.
IFX therapy has opposite effects in Foxp3(+) Treg cells in blood and gut mucosa, which suggests a redistribution of this important T-cell subset.
免疫疗法可能通过调节调节性 T 细胞（Tregs）在炎症性肠病（IBD）中发挥作用。因此，我们研究了英夫利昔单抗（IFX）治疗对克罗恩病（CD）和溃疡性结肠炎（UC）患者血液和肠道黏膜中叉头框蛋白 3（Foxp3）T 细胞的影响。
40 例活动性 IBD 患者（23 例 CD/17 例 UC）接受 IFX 5mg/kg 静脉滴注，分别在 0、2、6 周和此后每 8 周一次。在每次输注前采集血样，并通过流式细胞术对 T 淋巴细胞亚群进行特征分析。通过定量逆转录聚合酶链反应和免疫组织化学评估 43 例活动性 IBD 患者（19 例 CD/24 例 UC）在 IFX 输注前后和 6 例对照者的肠道活检中 Foxp3 的表达。同时收集血浆 C 反应蛋白（CRP）、临床反应和内镜愈合数据。
IFX 治疗导致外周血中 CD4+CD25+Foxp3+Treg 和 CD4+CD25-Foxp3+Treg 细胞的相对显著和持续增加（与基线相比，均 P<0.0001），特别是在应答者中（与无应答者相比，均 P<0.05）。CRP 随时间的变化与 CD25+Foxp3+细胞的增加呈负相关（P<0.001，r=-0.39），持久的临床应答与循环 Foxp3+细胞的持续增加相关。令人惊讶的是，IFX 治疗下调了 UC 和 CD 应答者肠道黏膜 Foxp3 的 mRNA 和蛋白表达（均 P<0.001），但在无应答者中无此作用。
IFX 治疗在血液和肠道黏膜中的 Foxp3+Treg 细胞中具有相反的作用，这表明该重要 T 细胞亚群的重新分布。
