Department of Food Science, University of Guelph, ON, Canada.
Clin Exp Allergy. 2010 Apr;40(4):668-78. doi: 10.1111/j.1365-2222.2009.03442.x. Epub 2010 Jan 14.
Peptide-based immunotherapy (PIT) represents an attractive approach for targeted interventions in immunological disorders, but has not been widely explored in the context of food allergy.
In this study, we built on the information obtained from the recent identification of three immunodominant T cell epitopes of hen ovalbumin (OVA), a major egg allergen, to assess the therapeutic potential of PIT for food allergy, using the BALB/c mouse model.
Groups of mice were sensitized to OVA by repeated oral gavages, and subsequently administered with single or multiple synthetic peptides containing OVA T cell epitopes. Following the peptide administration period, all mice were orally challenged with high doses of OVA to elicit active anaphylaxis. Serum, spleen, and intestinal tissues were collected for the determination of immunoglobulin levels, cytokine secretions, and intestinal gene expression.
Significantly lower anaphylactic scores were exhibited by mice that received multiple epitope-containing peptides, accompanied by lower serum histamine and OVA-specific IgE levels, compared with placebo-treated mice. Mechanistically, the quantification of cytokine secretions in splenocyte cultures revealed a T helper type 1-biased response (IFN-gamma) in all peptide-treated mice to the detriment of a T helper type 2-response (IL-4). Interestingly, a similar cytokine expression profile was determined in intestinal tissues, accompanied by a pronounced mRNA expression of regulatory molecules TGF-beta and forkhead box transcription factor 3 (FOXP3). These data suggest the activation of local repressive mechanisms mediated by subsets of regulatory T cells.
We demonstrated the therapeutic potential of PIT in a mouse model of food allergy model and provided evidence that mechanistic pathways entailing regulatory molecules TGF-beta and FOXP3, stand as promising trails for the further understanding of peptide-based strategies for food allergy.
基于肽的免疫疗法（PIT）代表了一种针对免疫性疾病的靶向干预的有吸引力的方法，但在食物过敏的背景下尚未得到广泛探索。
在这项研究中，我们基于最近鉴定的三种鸡卵清蛋白（OVA）免疫优势 T 细胞表位的信息，使用 BALB/c 小鼠模型，评估 PIT 用于食物过敏的治疗潜力。OVA 是一种主要的鸡蛋过敏原。
通过重复口服灌胃使小鼠致敏于 OVA，然后给予含有 OVA T 细胞表位的单一或多种合成肽。在肽给药期后，所有小鼠均用高剂量 OVA 口服挑战以引发主动过敏反应。收集血清、脾脏和肠道组织以确定免疫球蛋白水平、细胞因子分泌和肠道基因表达。
与安慰剂治疗的小鼠相比，接受多个含表位肽的小鼠表现出明显较低的过敏评分，同时血清组胺和 OVA 特异性 IgE 水平也较低。从机制上讲，在所有肽处理的小鼠的脾细胞培养物中定量细胞因子分泌显示出 Th1 偏向反应（IFN-γ），而不是 Th2 反应（IL-4）。有趣的是，在肠道组织中确定了类似的细胞因子表达谱，并伴有调节分子 TGF-β和叉头框转录因子 3（FOXP3）的明显 mRNA 表达。这些数据表明，由调节性 T 细胞亚群介导的局部抑制机制被激活。
我们在食物过敏模型的小鼠模型中证明了 PIT 的治疗潜力，并提供了证据表明，涉及调节分子 TGF-β和 FOXP3 的机制途径为进一步了解基于肽的食物过敏策略提供了有希望的线索。
