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Immunotherapy with oligomannose-coated liposomes ameliorates allergic symptoms in a murine food allergy model

机译:寡糖甘露糖衣脂质体的免疫疗法可改善鼠类食物过敏模型中的过敏症状

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Background: Allergen-specific immunotherapy has been anticipated to be a disease-modifying therapy for food allergies. We previously reported that CD8 + regulatory T cells may prevent antigen-sensitized mice from developing allergic diarrhea. Because oligomannose-coated liposomes (OML) have been shown to induce MHC class I-restricted CD8 + T cell responses, we analyzed the adjuvant activities of OML for inducing regulatory CD8 + T cells and mucosal tolerogenic responses in allergen-sensitized mice. Methods: The BALB/c mice that were previously sensitized to ovalbumin (OVA) were intranasally immunized with OVA-encased in OML (OVA-OML) or OVA-encased in non-coated liposomes (OVA-NL). We assessed allergic diarrhea induced by oral OVA administration, OVA-specific immunoglobulin production, and cytokine production in the intestines and mesenteric lymph nodes (MLNs). Results: Intranasal immunization with OVA-OML, but not OVA-NL, suppressed the development of allergic diarrhea. This was associated with in vitro Ag-induced IL-10 production and the in vivo expansion of CD8 + CD28 - and CD4 + CD25 + Foxp3 + T cell populations among mesenteric lymph node mononuclear cells, and was significantly ablated by anti-SIGNR1 or anti-CR3 mAbs. Up-regulation of serum OVA-specific IgE was suppressed, whereas OVA-specific IgG1, IgG2a, and soluble IgA production were enhanced by intranasal administration of OVA-OML. Adoptive transfer of CD8 + CD28 - T cells but not CD28 + CD8 + T cells from the MLNs of OVA-OML-treated mice ameliorated the development of diarrhea. Conclusion: These results suggest that intranasal immunization with Ag-encased OML may be an effective immunotherapy for food allergies, as it induces a subset of regulatory CD8 + T cells as well as CD4 + CD25 + Foxp3 + T cell and modulates humoral immune responses in allergen-sensitized mice.
机译:背景:过敏原特异的免疫疗法已被预料为食物过敏的疾病缓解疗法。我们先前曾报道CD8 +调节性T细胞可能会阻止抗原敏感的小鼠发展过敏性腹泻。因为低聚甘露糖衣脂质体(OML)已显示出诱导MHC I类限制的CD8 + T细胞反应,所以我们分析了OML在诱导变应原致敏的小鼠中诱导调节性CD8 + T细胞和粘膜耐受性反应的佐剂活性。方法:对先前对卵白蛋白(OVA)敏感的BALB / c小鼠鼻腔内用OML包裹的OVA(OVA-OML)或OVA包裹的非包衣脂质体(OVA-NL)进行免疫。我们评估了口服口服OVA,OVA特异性免疫球蛋白的产生以及肠和肠系膜淋巴结(MLN)中细胞因子的产生所致的过敏性腹泻。结果:用OVA-OML进行鼻内免疫,而不使用OVA-NL进行鼻内免疫,可以抑制过敏性腹泻的发展。这与体外Ag诱导的IL-10产生以及肠系膜淋巴结单核细胞中CD8 + CD28-和CD4 + CD25 + Foxp3 + T细胞群体的体内扩增有关,并被抗SIGNR1或抗-CR3 mAb。鼻内施用OVA-OML可抑制血清OVA特异性IgE的上调,而OVA特异性IgG1,IgG2a和可溶性IgA的产生则得到增强。从OVA-OML处理的小鼠的MLN中过继转移CD8 + CD28-T细胞,而不转移CD28 + CD8 + T细胞,可改善腹泻的发生。结论:这些结果表明,用Ag包裹的OML鼻内免疫可能是一种对食物过敏的有效免疫疗法,因为它诱导了一部分调节性CD8 + T细胞以及CD4 + CD25 + Foxp3 + T细胞并调节了小鼠的体液免疫应答。过敏原致敏的小鼠。

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