Takahashi I, Iijima H, Katashima R, Itakura M, Kiyono H
Department of Mucosal Immunology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
J Immunol. 1999 Feb 1;162(3):1843-50.
A population of CD4+ alpha-beta+ T cells increases in the mucosal and peripheral lymphoid tissues of TCRalpha-chain-deficient mice with inflammatory bowel disease. The alpha-beta+ T cells, which produce predominantly IL-4, mediate the proliferation of colonic epithelial crypts and the infiltration of large numbers of IgA-producing plasma cells into the lamina propria of the colon. To examine whether enteric Ags were recognized by a population of monoclonal alpha-beta+ T cells leading to the intestinal inflammation, we examined the usage and clonotypes of TCR expressed by the alpha-beta+ T cells in TCRalpha-chain-deficient mice with inflammatory bowel disease. Analyses of immunoprecipitates by two dimensional electrophoresis and single-cell RT-PCR revealed that TCR of the alpha-beta+ T cells was a homodimer of beta-chains that was capable of recognizing luminal bacterial Ags. PCR single-strand conformation polymorphism analysis of TCR Vbeta transcripts revealed monoclonal accumulation of the alpha-beta+ T cells in the colonic lamina propria of the diseased mice. DNA sequencing revealed the accumulation of the alpha-beta+ T cells with the same CDR3 sequences in the colon. These findings suggest that the pathogenic CD4+ alpha-beta+ T cells expressing a homodimeric form of the TCRbeta-chains can be clonally expanded upon the stimulation with gut-derived Ags.
在患有炎症性肠病的TCRα链缺陷小鼠的黏膜和外周淋巴组织中，CD4⁺αβ⁺T细胞群体增加。主要产生IL-4的αβ⁺T细胞介导结肠上皮隐窝的增殖以及大量产生IgA的浆细胞浸润到结肠固有层。为了研究肠道抗原是否被一群单克隆αβ⁺T细胞识别从而导致肠道炎症，我们检测了患有炎症性肠病的TCRα链缺陷小鼠中αβ⁺T细胞所表达的TCR的使用情况和克隆型。通过二维电泳和单细胞RT-PCR对免疫沉淀产物进行分析，结果显示αβ⁺T细胞的TCR是β链的同型二聚体，能够识别肠腔细菌抗原。对TCR Vβ转录本进行PCR单链构象多态性分析，结果显示患病小鼠结肠固有层中αβ⁺T细胞呈单克隆聚集。DNA测序显示结肠中具有相同CDR3序列的αβ⁺T细胞发生聚集。这些发现表明，表达TCRβ链同型二聚体形式的致病性CD4⁺αβ⁺T细胞在受到肠道来源抗原刺激后可发生克隆性扩增。
