Changes in human mucosal gamma delta T cell repertoire and function associated with the disease process in inflammatory bowel disease

Changes in human mucosal gamma delta T cell repertoire and function associated with the disease process in inflammatory bowel disease
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DOI:
10.1007/bf03401672
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发表时间:
1997-03-01
期刊:
影响因子:
5.7
通讯作者:
Carding, SR
Carding, SR
中科院分区:
医学2区
文献类型:
--
作者:
McVay, LD;Li, BQ;Carding, SR

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背景:虽然Gamma Delta T细胞是人类肠粘膜的主要组成部分,但它们在黏膜免疫中的作用以及它们是否参与炎症性肠病(IBD)的发病过程尚不清楚。材料和方法:采用流式细胞术和逆转录聚合酶链式反应(RT-PCR)检测溃疡性结肠炎(UC)和克罗恩病(CD)患者正常和(或)炎症性结肠组织标本中Gamma Delta T细胞的数量和质量的变化。细胞因子的产生和与结肠成纤维细胞的黏附和相互作用被用来比较从正常和病变的结肠粘膜分离的Gamma Delta T细胞的功能特性。结果:无论IBD的类型如何,大多数患者都发现定位于炎症和组织损伤区域的Gamma Delta T细胞数量增加。这种扩大是由于表达V delta1-(D Delta3)-J delta1编码的T细胞受体的V delta1(+)细胞增加,并在严重疾病以及新诊断或较轻形式的IBD患者中可见。CD患者炎症黏膜中的T细胞中,γ-Delta T细胞,尤其是V-Delta 1(+)细胞是促炎细胞因子--干扰素-γ的主要来源,并可与结肠成纤维细胞相互作用。结论:IBD慢性炎症免疫反应特征与粘膜γ-Delta T细胞的数量、分布、组成和功能发生明显变化有关。通过细胞因子的产生和与其他细胞的物理相互作用,γ-增量T细胞可以发挥免疫调节功能,参与IBD的病理生理过程。
Background: Although gamma delta T cells are a major component of the human intestinal mucosa, it is not clear what role they play in mucosal immunity or if they are involved in the disease process of inflammatory bowel disease (IBD).Materials and Methods: Flow cytometry and reverse transcriptase-polymerase chain reaction (RT-PCR) assays were used to identify quantitative and qualitative changes in the repertoire of gamma delta T cells present in surgical and/or biopsy samples of normal and inflamed colon from individual patients with ulcerative colitis (UC) or Crohn's disease (CD). Cytokine production and the ability to adhere to and interact with colonic fibroblasts were used to compare the functional properties of gamma delta T cells isolated from the normal and diseased colonic mucosa.Results: Increased numbers of gamma delta T cells localized in areas of inflammation and tissue injury were found in the majority of patients, irrespective of the type of IBD present. This expansion was attributable to an increase in V delta 1(+) cells expressing a V delta 1-(D delta 3)-J delta 1-encoded T cell receptor and was seen in patients with severe disease as well as those with newly diagnosed or less severe forms of IBD. Among T cells present in the inflamed mucosa of patients with CD, gamma delta T cells, particularly V delta 1(+) cells, were a major source of the proinflammatory cytokine interferon-gamma and could interact with colonic fibroblasts.Conclusions: Our results demonstrate that the chronic inflammatory immune response characteristic of IBD is associated with distinct changes in the number, distribution, composition, and function of mucosal gamma delta T cells. Through the production of cytokines and physical interaction with other cells, gamma delta T cells can perform an immunoregulatory function and contribute to the pathophysiology of IBDs.