Department of Food Science and Technology, College of Bioresource Sciences, Nihon University, 1866 Kameino, Fujisawa-shi, Kanagawa, 252-8510, Japan.
Cytotechnology. 2007 Dec;55(2-3):89-101. doi: 10.1007/s10616-007-9104-1. Epub 2007 Nov 1.
The development of allergy is related to differences in the intestinal microbiota. Therefore, it is suggested that the immune responses induced by different genera of bacteria might be regulated through adaptive as well as innate immunity. In this study, we examined whether antigen-specific immune responses were affected by stimulation with the different genera of intestinal bacteria in vitro. Mesenteric lymph node (MLN) cells isolated from germ-free ovalbumin (OVA)-specific T cell receptor transgenic (OVA-Tg) mice were stimulated with OVA and intestinal bacteria. Cecal contents from conventional mice but not germ-free mice could induce OVA-specific cytokine production. Among the murine intestinal bacteria, Bacteroides acidofaciens (BA) enhanced OVA-specific IFN-gamma and IL-10 production while Lactobacillus johnsonii (LA) increased OVA-specific IL-10 production only. The expression of cell surface molecules and cytokine production by antigen-presenting cells (APCs) from germ-free Balb/c mice were analyzed. BA increased the expression of MHC II and co-stimulatory molecules on APCs compared with LA. BA increased IL-6 and IL-10 production but induced less IL-12p40 than LA. To examine the effects of prior stimulation of APCs by intestinal bacteria on the induction of antigen-specific immune responses, cytokine production was determined following co-culture with OVA, CD4(+) T cells from OVA-Tg mice, and APCs which were pre-stimulated with the bacteria or not. APCs pre-stimulated with LA did not enhance OVA-specific cytokine production while BA stimulated OVA-specific IL-10 production. These results suggest that the prior stimulation of intestinal immunocytes by Lactobacillus might regulate excessive antigen-specific cytokine responses via APCs when compared with prior stimulation by Bacteroides.
过敏的发展与肠道微生物群的差异有关。因此，有人建议，不同属细菌诱导的免疫反应可能通过适应性和先天免疫来调节。在这项研究中，我们研究了体外刺激不同属肠道细菌是否会影响抗原特异性免疫反应。从无菌卵清蛋白（OVA）特异性 T 细胞受体转基因（OVA-Tg）小鼠的肠系膜淋巴结（MLN）细胞中分离出 MLN 细胞，并用 OVA 和肠道细菌刺激。常规小鼠而非无菌小鼠的盲肠内容物可诱导 OVA 特异性细胞因子产生。在鼠肠道细菌中，拟杆菌属（BA）增强了 OVA 特异性 IFN-γ和 IL-10 产生，而嗜酸乳杆菌（LA）仅增加了 OVA 特异性 IL-10 产生。分析了无菌 Balb/c 小鼠抗原呈递细胞（APC）的表面分子表达和细胞因子产生。与 LA 相比，BA 增加了 APC 上 MHC II 和共刺激分子的表达。BA 增加了 IL-6 和 IL-10 的产生，但诱导的 IL-12p40 少于 LA。为了研究 APC 预先通过肠道细菌刺激对诱导抗原特异性免疫反应的影响，通过与 OVA、来自 OVA-Tg 小鼠的 CD4(+)T 细胞和未预先用细菌刺激或预先用细菌刺激的 APC 共培养，确定细胞因子的产生。LA 预先刺激的 APC 不会增强 OVA 特异性细胞因子的产生，而 BA 刺激 OVA 特异性 IL-10 的产生。这些结果表明，与 Bacteroides 相比，Lactobacillus 对肠道免疫细胞的预先刺激可能通过 APC 调节过度的抗原特异性细胞因子反应。
