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葡萄球菌肠毒素A在成年小鼠对髓鞘碱性蛋白产生口服耐受中的作用。

The role of Staphylococcal enterotoxin A in achieving oral tolerance to myelin basic protein in adult mice.

作者信息

Miron Nicolae, Feldrihan Vasile, Berindan-Neagoe Ioana, Cristea Victor

机构信息

Department of Immunology, University of Medicine and Pharmacy "Iuliu Haţieganu" , Cluj-Napoca , Romania .

出版信息

Immunol Invest. 2014;43(3):267-77. doi: 10.3109/08820139.2013.868474. Epub 2013 Dec 19.

DOI:10.3109/08820139.2013.868474
PMID:24354887
Abstract

BACKGROUND

Oral tolerance is the biological process explaining the non-responsiveness of gut lymphoid tissue to intestinal content. Our study tested a new approach for the enhancement of oral tolerance to a multiple sclerosis-triggering auto-antigen-myelin basic protein, by its oral administration with the Staphylococcal enterotoxin A.

METHODS

Immune tolerance thus stimulated was assessed in adult BALB/c mice, by measuring different cytokines from the supernatant of mesenteric lymph nodes cells (IFN-γ, IL-4, IL-10, IL-17, and TGF-β), and in a SJL/E mouse model of experimental autoimmune encephalomyelitis, by evaluating the development of regulatory T cells in mesenteric lymph nodes and the clinical outcome of the intervention.

RESULTS

We obtained a significant rise in the levels of IL-10 and TGF-β compared with control and a significant decrease of IFN-γ, IL-4 (p < 0.05). Regulatory T cells were increased compared with control (p < 0.05). These results were attributable both to myelin basic protein and to Staphylococcal enterotoxin A. The clinical outcome of experimental autoimmune encephalomyelitis was influenced only by the administration of myelin basic protein.

CONCLUSION

In our experiment, Staphylococcal enterotoxin A enhanced the immune tolerance to myelin basic protein in the gut mucosa, but had no impact on the clinical evolution of experimental autoimmune encephalomyelitis.

摘要

背景

口服耐受是一种生物学过程,可解释肠道淋巴组织对肠内容物无反应的现象。我们的研究测试了一种新方法,即通过将葡萄球菌肠毒素A与引发多发性硬化症的自身抗原——髓鞘碱性蛋白一起口服,来增强对其的口服耐受。

方法

通过测量肠系膜淋巴结细胞上清液中的不同细胞因子(IFN-γ、IL-4、IL-10、IL-17和TGF-β),在成年BALB/c小鼠中评估由此刺激产生的免疫耐受;在实验性自身免疫性脑脊髓炎的SJL/E小鼠模型中,通过评估肠系膜淋巴结中调节性T细胞的发育情况以及干预的临床结果来进行评估。

结果

与对照组相比,我们发现IL-10和TGF-β水平显著升高,IFN-γ、IL-4水平显著降低(p < 0.05)。与对照组相比,调节性T细胞增加(p < 0.05)。这些结果既归因于髓鞘碱性蛋白,也归因于葡萄球菌肠毒素A。实验性自身免疫性脑脊髓炎的临床结果仅受髓鞘碱性蛋白给药的影响。

结论

在我们的实验中,葡萄球菌肠毒素A增强了肠道黏膜对髓鞘碱性蛋白的免疫耐受,但对实验性自身免疫性脑脊髓炎的临床进展没有影响。

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The role of Staphylococcal enterotoxin A in achieving oral tolerance to myelin basic protein in adult mice.葡萄球菌肠毒素A在成年小鼠对髓鞘碱性蛋白产生口服耐受中的作用。
Immunol Invest. 2014;43(3):267-77. doi: 10.3109/08820139.2013.868474. Epub 2013 Dec 19.
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IL-4 is a differentiation factor for transforming growth factor-beta secreting Th3 cells and oral administration of IL-4 enhances oral tolerance in experimental allergic encephalomyelitis.白细胞介素-4是分泌转化生长因子-β的Th3细胞的分化因子,口服白细胞介素-4可增强实验性变应性脑脊髓炎中的口服耐受性。
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Suppressor T cells generated by oral tolerization to myelin basic protein suppress both in vitro and in vivo immune responses by the release of transforming growth factor beta after antigen-specific triggering.通过口服髓鞘碱性蛋白诱导产生的抑制性T细胞,在抗原特异性触发后通过释放转化生长因子β,在体外和体内均抑制免疫反应。
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Oral administration of the bacterial superantigen staphylococcal enterotoxin B induces activation and cytokine production by T cells in murine gut-associated lymphoid tissue.口服细菌超抗原葡萄球菌肠毒素B可诱导小鼠肠道相关淋巴组织中的T细胞活化并产生细胞因子。
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