Oligoclonal Th2-biased ΒΒ T cells induce murine inflammatory bowel disease

Oligoclonal Th2-biased ΒΒ T cells induce murine inflammatory bowel disease
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寡克隆 Th2 偏向 ΒΒ T 细胞诱导小鼠炎症性肠病

DOI:
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发表时间:
1999
期刊:
影响因子:
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通讯作者:
H. Kiyono
H. Kiyono
中科院分区:
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文献类型:
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作者:
I. Takahashi;H. Lijima;D. Kishi;H. Kiyono

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在患有炎性肠病(IBD)的TCR α链缺陷小鼠的粘膜和外周组织中,产生Th 2型细胞因子的具有TCR β链而不具有TCR α链的CD 4 + T细胞(CD 4+,BB T细胞)群体增加。通过双向电泳和RT-PCR分析TCR-B免疫沉淀物,显示CD 4 + T细胞的TCR是TCR Β-链的同源二聚体。BBT细胞的TCR V β链转录物的聚合酶链反应-单链构象多态性(PCR-SSCP)分析揭示了细胞在结肠中的单克隆至寡克隆积累,表明在用肠源性抗原刺激时粘膜BBT细胞的克隆扩增。BBT细胞上TCR B链的同源二聚体是生物学功能受体,其转导由MHC II类相关肽抗原和超抗原提供的活化信号。用抗TCR B或IL-4的mAb治疗突变小鼠抑制IBD的发作。这些发现表明寡克隆Th 2型BBT细胞的产生在IBD的发展中起关键作用。
A population of CD4+ T cells with TCR Β-chain without TCR a-chain (CD4+, ΒΒ 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+ T cells was a homodimer of TCR Β-chains. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analyses of TCR VΒ-chain transcripts of the ΒΒ T cells revealed monoclonal to oligoclonal accumulation of the cells in the colon, suggesting clonal expansion of the mucosal ΒΒ T cells upon the stimulation with gut-derived antigens. The homodimer of TCR Β-chains on the ΒΒ T cells was a biologically functional receptor that transduced activation signals provided by MHC-class II-associated peptidic antigens and superantigens. Treatments of the mutant mice with mAb against TCR Β or IL-4 suppressed the onset of IBD. These findings suggest that the generation of oligoclonal Th2-type ΒΒ T cells plays a critical role for the development of IBD.
DOI: 10.1016/s0016-5085(99)70128-9
发表时间: 1999-02-01
期刊: GASTROENTEROLOGY
影响因子: 29.4
作者:
Mizoguchi, A;Mizoguchi, E;Bhan, AK
通讯作者: Bhan, AK