Oral administration of schistosome egg antigens and insulin B-chain generates and enhances Th2-type responses in NOD mice.
Oral administration of schistosome egg antigens and insulin B-chain generates and enhances Th2-type responses in NOD mice.
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DOI：
10.1006/clin.1997.4506
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发表时间：
1998-04
期刊：
影响因子：
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通讯作者：
R. Maron;V. Palanivel;H. Weiner;D. Harn
中科院分区：
文献类型：
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作者：
R. Maron;V. Palanivel;H. Weiner;D. Harn
在小鼠曼氏血吸虫中，寄生虫卵或盐水可溶性卵抗原（SEA）的胃肠外给药可产生对寄生虫体特异性和无关第三方抗原的Th2 T细胞应答。NOD小鼠口服胰岛素通过使对CD4 + Th2细胞和TGF-β产生细胞的反应发生偏移来抑制或延迟糖尿病的发作。从这两组独立的观察结果，我们开始了本研究，以确定如果口服SEA将刺激Th2型细胞因子的反应时，小鼠喂养SEA单独或串联与胰岛素B链。我们的研究结果表明，无论是胰岛素B链或SEA单独喂养NOD小鼠显着抑制增殖的免疫抗原。当检查细胞因子谱时，喂食导致IL-10和TGF-β产生占优势。此外，喂养SEA与胰岛素B链的组合增加了IL-10产生胰岛素的水平。从SEA喂养和免疫的小鼠建立的T细胞系分泌IL-4和IL-10细胞因子，而从对照喂养的SEA免疫的小鼠建立的T细胞系主要分泌IL-2和IFN-γ。这些结果表明，口服给药的胰岛素可以诱导分泌IL-4、IL-10和TGF-β的调节性T细胞，并且通过一起饲喂SEA和胰岛素B链，可以以协同方式增强对口服胰岛素的Th2应答。
In murine Schistosoma mansoni, parenteral administration of parasite eggs or saline-soluble egg antigens (SEA), generates Th2 T-cell responses to both schistosome-specific and unrelated third-party antigens. Oral administration of insulin to NOD mice suppresses or delays the onset of diabetes by skewing the response toward CD4+ Th2 cells and TGF-beta producing cells. From these two independent sets of observations, we initiated the present study to determine if oral administration of SEA would stimulate Th2-type cytokine responses when mice were fed SEA alone or in tandem with insulin B-chain. Our results show that feeding NOD mice with either insulin B-chain or SEA alone significantly inhibits proliferation to the immunizing antigen. When cytokine profiles were examined, feeding led to a predominance of IL-10 and TGF-beta production. Furthermore, feeding SEA in combination with insulin B-chain augmented the level of IL-10 production to insulin. T-cell lines established from SEA-fed and -immunized mice secreted IL-4 and IL-10 cytokines whereas the T-cell lines from control-fed mice immunized with SEA secreted predominantly IL-2 and IFN-gamma. These results demonstrate that orally administered insulin can induce regulatory T-cells secreting IL-4, IL-10, and TGF-beta and that Th2 responses to oral insulin could be augmented in a synergistic way by feeding SEA and insulin B-chain together.