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Molecular biology of oligoclonal ββィイD1+ィエD1 T cells in murine inflammatory bowel disease

小鼠炎症性肠病寡克隆 ββD1+D1 T 细胞的分子生物学

基本信息

批准号：
10670302
负责人：
TAKAHASHI Ichiro
金额：
$ 1.66万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670302/
关键词：
ββ T cells Th2 cytokine IBD mucosal T cells clonality gut-flora PCR-SSCP TCR beta beta クロナリティ-腸内細菌

项目摘要

A population of CD4ィイD1+ィエD1 T cells with TCR β-chain without TCR α-chain (CD4ィイD1+ィエD1,ββィイD1+ィエD1 T cells) producing Th2-type cytokines increased in the mucosal and peripheral tissues of TCR α-chain deficient mice with inflammatory bowel disease (IBD). Analysis of TCR-β immunoprecipitates by two-dimensional electrophoresis and RT-PCR revealed TCR of the CD4ィイD1+ィエD1 T cells was a homodimer of TCR β-chains. PCR-SSCP analyses of TCR νβ-chain transcripts of the ββィイD1+ィエD1 T cells revealed monoclonal to oligoclonal accumulation of the cells in the colon, suggestingclonal expansion of the mucosal ββィイD1+ィエD1 T cells upon the stimulation with gut-derived antigens. The homodimer of TCR β-chains on the ββィイD1+ィエD1 T cells was a biologically functional receptor which transducedactivation signals provided by MHC-class ll-associated peptidic antigens and superantigens. The importance of the Th2-biased ββィイD1+ィエD1 T cells was also supported by the finding that treatments of the mutant mice with mAb against TCR βor lL-4 suppressed the onset of IBD. The Th2-biased cytokine production by the ββィイD1+ィエD1 T cells in IBD mice could be attributed to the high incidence of Bacteroides vulgatus. Rectal administration of non-diseased mice with B. vulgatus resulted in the development of Th2-type ββィイD1+ィエD1 T cell-induced colitis. These findings suggest that the generation of oligoclonal Th2-type ββィイD1+ィエD1 T cells plays a critical role for the development of IBD.

在炎性肠病（IBD）TCR α链缺陷小鼠的粘膜和外周组织中，产生Th 2型细胞因子的CD 4 + CD 4D 1 + CD 4D 1 + T细胞（CD 4 + CD 4D 1 + CD 4D 1，ββ CD 4D 1 + CD 4D 1 + T细胞）数量增加。经双向电泳和RT-PCR分析，CD 4 + CD 4 + CD 4 + CD 4 + D1 T细胞的TCR-β免疫沉淀物为TCR β链的同源二聚体。对ββ CD 3D 1 + CD 3D 1 T细胞TCR v β链转录物的PCR-SSCP分析揭示了细胞在结肠中的单克隆至寡克隆积累，从而阻止了粘膜β CD 3D 1 + CD 3D 1 T细胞在肠源性抗原刺激后的克隆扩增。ββ受体D1+ β受体D1 T细胞上TCR β链的同源二聚体是一种生物学功能受体，可传递MHC Ⅱ类相关肽抗原和超抗原提供的活化信号。Th 2-偏向的ββ CD 3D 1 + CD 3D 1 T细胞的重要性也得到以下发现的支持，即用针对TCR β或IL-4的mAb治疗突变小鼠抑制IBD的发作。IBD小鼠中ββ-IFN-γ D1+ IFN-γ D1 T细胞的Th 2偏向性细胞因子产生可归因于普通拟杆菌的高发病率。用B直肠给药未患病小鼠。普通小鼠导致Th 2型ββイD1+ D1 T细胞诱导的结肠炎的发生。这些发现表明寡克隆Th 2型ββ CD 1D 1 + CD 1D 1 T细胞的产生在IBD的发展中起着关键作用。