A rice-based edible vaccine expressing multiple T cell epitopes induces oral tolerance for inhibition of Th2-mediated IgE responses.
A rice-based edible vaccine expressing multiple T cell epitopes induces oral tolerance for inhibition of Th2-mediated IgE responses.
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DOI：
10.1073/pnas.0503428102
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发表时间：
2005-11
影响因子：
11.1
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中科院分区：
文献类型：
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使用多种主要变应原特异性T细胞表位的肽免疫治疗是控制I型变态反应的安全且有前途的策略。在这项研究中，我们开发了转基因水稻植物表达小鼠显性T细胞表位肽的Cry j I和Cry j II过敏原的日本雪松花粉作为融合蛋白与大豆种子贮藏蛋白大豆球蛋白。在水稻种子贮藏蛋白GluB-1启动子的控制下，融合蛋白在种子中特异性表达并积累，其水平为种子总蛋白的0.5%。在用雪松花粉总蛋白全身攻击之前，口服表达Cry j I和Cry j II的T细胞表位肽的转基因水稻种子抑制过敏原特异性血清IgE和IgG抗体以及CD 4（+）T细胞增殖反应的产生。过敏原特异性CD 4（+）T细胞衍生的过敏相关辅助性T细胞2细胞因子IL-4、IL-5和IL-13的产生水平以及血清中组胺的释放水平显著降低。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被抑制。这些结果表明，潜在的转基因水稻种子在生产和粘膜传递过敏原特异性T细胞表位肽诱导口服耐受花粉过敏原。
Peptide 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 peptides 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 peptides for the induction of oral tolerance to pollen allergens.