Smaldini Paola Lorena, Orsini Delgado María Lucía, Fossati Carlos Alberto, Docena Guillermo Horacio
Instituto de Estudios Inmunológicos y Fisiopatológicos-IIFP, Facultad de Ciencias Exactas, Universidad Nacional de La Plata y Consejo Nacional de Investigaciones Científicas y Técnicas, La Plata, Argentina.
PLoS One. 2015 Oct 30;10(10):e0141116. doi: 10.1371/journal.pone.0141116. eCollection 2015.
The induction of peripheral tolerance may constitute a disease-modifying treatment for allergic patients. We studied how oral immunotherapy (OIT) with milk proteins controlled allergy in sensitized mice (cholera toxin plus milk proteins) upon exposure to the allergen. Symptoms were alleviated, skin test was negativized, serum specific IgE and IgG1 were abrogated, a substantial reduction in the secretion of IL-5 and IL-13 by antigen-stimulated spleen cells was observed, while IL-13 gene expression in jejunum was down-regulated, and IL-10 and TGF-β were increased. In addition, we observed an induction of CD4+CD25+FoxP3+ cells and IL-10- and TGF-β-producing regulatory T cells in the lamina propria. Finally, transfer experiments confirmed the central role of these cells in tolerance induction. We demonstrated that the oral administration of milk proteins pre- or post-sensitization controlled the Th2-immune response through the elicitation of mucosal IL-10- and TGF-β-producing Tregs that inhibited hypersensitivity symptoms and the allergic response.
诱导外周耐受可能构成一种针对过敏患者的疾病改善疗法。我们研究了用牛奶蛋白进行口服免疫疗法（OIT）如何在致敏小鼠（霍乱毒素加牛奶蛋白）接触过敏原后控制过敏反应。症状得到缓解，皮肤试验转阴，血清特异性IgE和IgG1消失，观察到抗原刺激的脾细胞分泌的IL-5和IL-13大幅减少，同时空肠中IL-13基因表达下调，IL-10和TGF-β增加。此外，我们在固有层观察到CD4+CD25+FoxP3+细胞以及产生IL-10和TGF-β的调节性T细胞的诱导。最后，转移实验证实了这些细胞在耐受诱导中的核心作用。我们证明，在致敏前或致敏后口服牛奶蛋白可通过诱导产生黏膜IL-10和TGF-β的调节性T细胞来控制Th2免疫反应，这些调节性T细胞可抑制过敏症状和过敏反应。
