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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >A rice-based edible vaccine expressing multiple T cell epitopes induces oral tolerance for inhibition of Th2-mediated IgE responses
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A rice-based edible vaccine expressing multiple T cell epitopes induces oral tolerance for inhibition of Th2-mediated IgE responses

机译：一种基于水稻的可表达多种T细胞表位的疫苗可诱导口服抑制Th2介导的IgE反应的耐受性

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摘要

Pepticle immunotherapy using multiple predominant allergen-specific T cell epitopes is a safe and promising strategy for the control of type I allergy. In this study, we developed transgenic rice plants expressing mouse dominant T cell epitope peptides of Cry j I and Cry j II allergens of Japanese cedar pollen as a fusion protein with the soybean seed storage protein glycinin. Under the control of the rice seed storage protein glutelin GluB-1 promoter, the fusion protein was specifically expressed and accumulated in seeds at a level of 0.5% of the total seed protein. Oral feeding to mice of transgenic rice seeds expressing the T cell epitope pepticles of Cry j I and Cry j II before systemic challenge with total protein of cedar pollen inhibited the development of allergen-specific serum IgE and IgG antibody and CD4(+) T cell proliferative responses. The levels of allergen-specific CD4(+) T cell-derived allergy-associated T helper 2 cytokine production of IL-4, IL-5, and IL-13 and histamine release in serum were significantly decreased. Moreover, the development of pollen-induced clinical symptoms was inhibited in our experimental sneezing mouse model. These results indicate the potential of transgenic rice seeds in production and mucosal delivery of allergen-specific T cell epitope pepticles for the induction of oral tolerance to pollen allergens.
机译：使用多种主要的过敏原特异性T细胞表位进行的消化性免疫疗法是控制I型过敏的安全且有希望的策略。在这项研究中，我们开发了转基因水稻植株，该植株表达了日本雪松花粉的Cry j I和Cry j II过敏原的小鼠优势T细胞表位肽，作为与大豆种子存储蛋白大豆球蛋白的融合蛋白。在水稻种子贮藏蛋白谷蛋白GluB-1启动子的控制下，融合蛋白被特异性表达并累积在种子中，其含量为种子蛋白总量的0.5％。口服饲喂表达雪松花粉总蛋白的Cry j I和Cry j II T细胞抗原决定簇的转基因水稻种子的小鼠，抑制了过敏原特异性血清IgE和IgG抗体以及CD4（+）T细胞的发育增殖反应。血清中IL-4，IL-5和IL-13的变应原特异性CD4（+）T细胞来源的变态反应相关的T辅助2细胞因子的水平显着降低。此外，在我们的实验性打喷嚏小鼠模型中，花粉诱导的临床症状的发展受到抑制。这些结果表明转基因水稻种子在生产和粘膜传递变应原特异性T细胞表位消化物方面具有潜在的诱导对花粉变应原的口服耐受性。

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