Nutrition Science Institute, Meiji Dairies Co., Ltd., 540, Naruda, Odawara, Kanagawa, Japan.
Cytotechnology. 2002 Nov;40(1-3):49-58. doi: 10.1023/A:1023962021081.
We have investigated the influence of dietary nucleotides on the intestinal immune system in ovalbumin (OVA)-specific T-cell receptor (TCR) transgenic mice (OVA-TCR Tg mice). When mice were supplied with water supplemented with 2% OVA ad libitum, the faecal OVA-specific immunoglobulin A (IgA) level significantly increased in those fed a nucleotide-supplemented diet (NT(+) diet) compared with those fed a nucleotide-free control diet (NT(-) diet). In the NT(+) diet-fed mice, secretion of transforming growth factor beta (TGF-beta), which is an isotype-specific switch factor for IgA, from intestinal epithelial cells (IECs) was significantly increased. Furthermore, an increased proportion of intestinal intraepithelial lymphocytes (IELs) bearing gammadelta TCR (TCRgammadelta(+) IELs) and increased secretion from IECs of interleukin 7 (IL-7), which is essential for the development of TCRgammadelta(+) IELs, were also observed in OVA-TCR-Tg mice fed the NT(+) diet, as we previously demonstrated using BALB/c mice (Nagafuchi et al., Biosci. Biotechnol. Biochem. 64: 1459-65 (2000)). Considering that TCRgammadelta(+) T cells and TGF-beta are important for an induction of the mucosal IgA response, our results suggest that dietary nucleotides augment the mucosal OVA-specific IgA response by increasing the secretion of TGF-beta from IECs and the proportion of TCRgammadelta(+) IELs.
我们研究了膳食核苷酸对卵清蛋白(OVA)特异性 T 细胞受体(TCR)转基因小鼠(OVA-TCR Tg 小鼠)肠道免疫系统的影响。当小鼠自由饮用添加 2%OVA 的水时,与食用不含核苷酸对照饮食(NT(-)饮食)的小鼠相比,食用含核苷酸饮食(NT(+)饮食)的小鼠粪便中 OVA 特异性免疫球蛋白 A(IgA)水平显著升高。在 NT(+)饮食喂养的小鼠中,肠道上皮细胞(IEC)转化生长因子β(TGF-β)的分泌显著增加,TGF-β是 IgA 的同种型转换因子。此外,与食用不含核苷酸对照饮食(NT(-)饮食)的小鼠相比,肠道上皮内淋巴细胞(IEL)中表达γδ TCR(TCRγδ(+)IEL)的比例增加,以及 IEC 中白细胞介素 7(IL-7)的分泌增加,而 IL-7 对于 TCRγδ(+)IEL 的发育是必需的,这些在 NT(+)饮食喂养的 OVA-TCR-Tg 小鼠中也观察到,正如我们之前使用 BALB/c 小鼠所证明的那样(Nagafuchi 等人,Biosci. Biotechnol. Biochem. 64: 1459-65(2000))。考虑到 TCRγδ(+)T 细胞和 TGF-β对于诱导黏膜 IgA 反应很重要,我们的结果表明,膳食核苷酸通过增加 IEC 中 TGF-β的分泌和 TCRγδ(+)IEL 的比例来增强黏膜 OVA 特异性 IgA 反应。