Kikuchi Akira, Nakajima-Adachi Haruyo, Ebihara Ayumi, Takahashi Yoshimasa, Hosono Akira, Itoh Kikuji, Hachimura Satoshi, Kaminogawa Shuichi
Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-8657, Japan.
Biofactors. 2004;21(1-4):159-62. doi: 10.1002/biof.552210132.
To investigate the mechanisms inducing food-sensitive intestinal inflammation, we focused on the OVA23-3 mouse, a transgenic mouse strain expressing a T cell receptor that recognizes ovalbumin (OVA). Mice administered an egg-white (EW) diet containing OVA showed a trend of loose feces and significant weight loss. Histology of the jejunum showed severe inflammation with villous atrophy. Thus, we studied the role of T cells and intestinal microflora in the development of the inflammation. Severe villous disruption was observed in sections of the jejunum from OVA23-3 mice and RAG-2 gene-deficient OVA23-3 mice fed with EW-diet. Further, a larger number of T cells was found in the lamina propria of the jejunum of EW-diet fed OVA23-3 mice, RAG-2 gene-deficient mice and germfree OVA23-3 mice compared with those of control-diet fed mice. However, severe inflammation was not detected in the jejunum of germfree OVA23-3 mice. CD4+ T cells from the MLN of EW-diet fed OVA23-3 mice showed a Th2 cytokine secretion profile. These observations have thus clarified that antigen-specific Th2 cells play important roles in the development of intestinal inflammation. Although the presence of indigenous bacteria was not essential for the inflammation, T cells could mediate a more severe inflammatory response in their presence.
为了研究引发食物敏感性肠道炎症的机制,我们重点研究了OVA23 - 3小鼠,这是一种表达识别卵清蛋白(OVA)的T细胞受体的转基因小鼠品系。给小鼠喂食含OVA的蛋清(EW)饮食后,小鼠出现粪便变稀的趋势并伴有显著体重减轻。空肠组织学检查显示有严重炎症伴绒毛萎缩。因此,我们研究了T细胞和肠道微生物群在炎症发展中的作用。给OVA23 - 3小鼠和RAG - 2基因缺陷的OVA23 - 3小鼠喂食EW饮食后,在它们空肠切片中观察到严重的绒毛破坏。此外,与喂食对照饮食的小鼠相比,在喂食EW饮食的OVA23 - 3小鼠、RAG - 2基因缺陷小鼠和无菌OVA23 - 3小鼠的空肠固有层中发现了更多的T细胞。然而,在无菌OVA23 - 3小鼠的空肠中未检测到严重炎症。喂食EW饮食的OVA23 - 3小鼠肠系膜淋巴结中的CD4 + T细胞表现出Th2细胞因子分泌谱。这些观察结果因此阐明了抗原特异性Th2细胞在肠道炎症发展中起重要作用。虽然本地细菌的存在对于炎症并非必不可少,但T细胞在其存在时可介导更严重的炎症反应。