Department of Microbiology, Immunology, and Cell Biology, Robert C. Byrd Health Sciences Center of West Virginia University, Morgantown, P.O. Box 9177, WV 26506, USA.
Immunobiology. 2010 Dec;215(12):941-8. doi: 10.1016/j.imbio.2010.02.004. Epub 2010 Mar 4.
IgE-mediated food allergies are an important cause of life-threatening hypersensitivity reactions. Orally administered peanut antigens mixed with the mucosal adjuvant cholera toxin (CT) induce a strong peanut extract (PE)-specific serum IgE response that is correlated with T-helper type 1 (Th1) and type 2 (Th2)-like T-cell responses. This study was conducted to determine if respiratory enteric orphan virus (reovirus), a non-pathogenic virus that induces robust Th1-mediated mucosal and systemic responses could modulate induction of PE-specific allergic responses when co-administered with PE. Young mice were orally exposed to PE mixed with CT, reovirus, or both CT and reovirus. As expected, CT promoted PE-specific serum IgE, IgG1, and IgG2a and intestinal IgA production as well as splenic Th1- and Th2-associated cytokine recall responses. Reovirus did not alter PE-specific serum IgE and IgG1 levels, but substantially increased the PE-specific IgG2a response when co-administered with PE with or without CT. Additionally, reovirus significantly decreased the percentage of the Peyer's patch CD8+ T-cells and Foxp3+CD4+ T-regulatory cells when co-administered with PE. These results demonstrate that an acute mucosal reovirus infection and subsequent Th1 immune response is capable of modulating the Th1/Th2 controlled humoral response to PE. The reovirus-mediated increase in the PE-specific IgG2a antibody response may have therapeutic implications as increased levels of non-allergenic PE-specific IgG2a could block PE antigens from binding to IgE-sensitized mast cells.
IgE 介导的食物过敏是危及生命的过敏反应的重要原因。口服给予与粘膜佐剂霍乱毒素(CT)混合的花生抗原会诱导强烈的花生提取物(PE)特异性血清 IgE 反应,该反应与辅助性 T 细胞 1(Th1)和 2(Th2)样 T 细胞反应相关。本研究旨在确定呼吸道肠道孤儿病毒(reovirus)是否可以调节 PE 特异性过敏反应的诱导,呼吸道肠道孤儿病毒是一种非致病性病毒,可诱导强烈的 Th1 介导的粘膜和全身反应,当与 PE 共同给予时。年轻的老鼠通过口服暴露于与 CT、reovirus 或 CT 和 reovirus 混合的 PE。正如预期的那样,CT 促进了 PE 特异性血清 IgE、IgG1 和 IgG2a 以及肠道 IgA 的产生以及脾 Th1 和 Th2 相关细胞因子的回忆反应。reovirus 没有改变 PE 特异性血清 IgE 和 IgG1 水平,但当与 PE 共同给予时,大大增加了 PE 特异性 IgG2a 反应,无论是否存在 CT。此外,reovirus 与 PE 共同给予时,可显著减少派尔集合淋巴结的 CD8+T 细胞和 Foxp3+CD4+T 调节细胞的百分比。这些结果表明,急性粘膜 reovirus 感染和随后的 Th1 免疫反应能够调节对 PE 的 Th1/Th2 控制的体液反应。reovirus 介导的 PE 特异性 IgG2a 抗体反应的增加可能具有治疗意义,因为增加的非过敏原性 PE 特异性 IgG2a 水平可以阻止 PE 抗原与 IgE 致敏的肥大细胞结合。