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肠易激综合征患者的T细胞活化

T-cell activation in patients with irritable bowel syndrome.

作者信息

Ohman Lena, Isaksson Stefan, Lindmark Ann-Charlotte, Posserud Iris, Stotzer P-O, Strid Hans, Sjövall Henrik, Simrén Magnus

机构信息

Department of Internal Medicine, Institute of Medicine, The Sahlgren's Academy, University of Gothenburg, Gothenburg, Sweden.

出版信息

Am J Gastroenterol. 2009 May;104(5):1205-12. doi: 10.1038/ajg.2009.116. Epub 2009 Apr 14.

DOI:10.1038/ajg.2009.116
PMID:19367268
Abstract

OBJECTIVES

Irritable bowel syndrome (IBS) has been found to be associated with low-grade immune activation in a subset of patients. We therefore investigated blood and colonic T-cell activity in IBS patients.

METHODS

Blood samples were initially obtained from 74 IBS patients and 30 controls. Supplementary blood samples, to confirm data, were taken from another cohort (26 patients and 14 controls). In addition, colonic biopsies were taken from a third cohort (11 patients and 10 controls). Peripheral blood and colonic mononuclear cells were stimulated with anti-CD3/CD28 antibodies. Proliferation, cytokine secretion, and T-cell phenotype were investigated. IBS symptom severity was assessed.

RESULTS

IBS patients displayed an activated phenotype with increased frequencies of blood T cells expressing CD69 and integrin beta7/HLA-DR. Anti-CD3/CD28-stimulated blood and colonic T cells from IBS patients proliferated less than T cells from controls. IBS patients had an increased polyclonally stimulated T-cell secretion of IL-1beta, which also weakly correlated with increased bowel habit dissatisfaction. Furthermore, despite normal frequencies of CD25high T cells in the blood of IBS patients, lower blood CD25high T-cell frequencies were modestly correlated with more bowel habit dissatisfaction and increased total IBS symptom severity.

CONCLUSIONS

IBS patients have an increased frequency of activated T cells, demonstrated by the expression of activation markers and reduced proliferation in response to restimulation in vitro. The increased level of T-cell activation is consistent with the hypothesis of low-grade immune activation in IBS and may also be involved in symptom generation in IBS.

摘要

目的

已发现肠易激综合征(IBS)在一部分患者中与低度免疫激活有关。因此,我们研究了IBS患者的血液和结肠T细胞活性。

方法

最初从74例IBS患者和30例对照中采集血样。为确认数据,从另一队列(26例患者和14例对照)采集补充血样。此外,从第三队列(11例患者和10例对照)获取结肠活检组织。用抗CD3/CD28抗体刺激外周血和结肠单个核细胞。研究细胞增殖、细胞因子分泌及T细胞表型。评估IBS症状严重程度。

结果

IBS患者表现出激活的表型,表达CD69和整合素β7/HLA-DR的血液T细胞频率增加。IBS患者经抗CD3/CD28刺激的血液和结肠T细胞增殖少于对照组T细胞。IBS患者多克隆刺激的T细胞分泌IL-1β增加,这也与肠道习惯不满意增加弱相关。此外,尽管IBS患者血液中CD25高表达T细胞频率正常,但较低的血液CD25高表达T细胞频率与更多的肠道习惯不满意及IBS总症状严重程度增加适度相关。

结论

IBS患者激活的T细胞频率增加,这通过激活标志物的表达及体外再次刺激时增殖减少得以证明。T细胞激活水平增加与IBS低度免疫激活假说一致,也可能参与IBS症状的产生。

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