Roman L I, Manzano L, De La Hera A, Abreu L, Rossi I, Alvarez-Mon M
Department of Medicine, Principe de Asturias Hospital, Alcalá University, Madrid, Spain.
Gastroenterology. 1996 Apr;110(4):1008-19. doi: 10.1053/gast.1996.v110.pm8612987.
BACKGROUND & AIMS: An abnormal immune response may play a pathogenic role in Crohn's disease. The aim of this study was to determine the role of regulatory T cells in Crohn's disease.
T-cell phenotype and function were studied in blood lymphocytes from patients with Crohn's disease and a control group consisting of healthy donors and patients with ulcerative colitis.
Flow cytometric studies showed a significant increase in the percentage of CD3+DR+ and CD4+CD45RO+ T cells in patients with Crohn's disease. T cells from patients with Crohn's disease and ulcerative colitis showed a defective proliferative response after stimulation with surface mitogenic ligands (phytohemagglutinin and anti-CD28 or anti-CD3 antibodies). Soluble interleukin-2 receptor alpha was augmented in the Crohn's disease and ulcerative colitis groups. In the Crohn's disease group, impairment of T-lymphocyte proliferation was normalized by exogenous interleukin 2, although endogenous interleukin-2 production and interleukin-2 receptor alpha expression were normal.
An in vivo expansion of CD4+ T lymphocytes with memory phenotype and impaired T-cell proliferation that can be restored by pharmacological amounts of interleukin 2 was found in patients with Crohn's disease. There is a severe immunodisturbance in the T-cell compartment of patients with either clinically active or inactive Crohn's disease.
异常免疫反应可能在克罗恩病中起致病作用。本研究旨在确定调节性T细胞在克罗恩病中的作用。
对克罗恩病患者以及由健康供者和溃疡性结肠炎患者组成的对照组的血液淋巴细胞进行T细胞表型和功能研究。
流式细胞术研究显示,克罗恩病患者中CD3+DR+和CD4+CD45RO+ T细胞百分比显著增加。克罗恩病患者和溃疡性结肠炎患者的T细胞在用表面促有丝分裂配体(植物血凝素和抗CD28或抗CD3抗体)刺激后显示出增殖反应缺陷。可溶性白细胞介素-2受体α在克罗恩病组和溃疡性结肠炎组中均升高。在克罗恩病组中,尽管内源性白细胞介素-2产生和白细胞介素-2受体α表达正常,但外源性白细胞介素-2可使T淋巴细胞增殖障碍恢复正常。
在克罗恩病患者中发现具有记忆表型的CD4+ T淋巴细胞在体内扩增且T细胞增殖受损,而药理剂量的白细胞介素-2可使其恢复。无论是临床活动期还是非活动期的克罗恩病患者,其T细胞区室均存在严重的免疫紊乱。