Kawabe Yoshinori, Hayashida Yuuki, Numata Kensaku, Harada Shota, Hayashida Yoshifumi, Ito Akira, Kamihira Masamichi
Department of Chemical Engineering, Faculty of Engineering, Kyushu University, Fukuoka, Japan.
PLoS One. 2012;7(10):e48512. doi: 10.1371/journal.pone.0048512. Epub 2012 Oct 29.
Peptide immunotherapy using T-cell epitopes is expected to be an effective treatment for allergic diseases such as Japanese cedar (Cryptomeria japonica; Cj) pollinosis. To develop a treatment for pollen allergy by inducing oral tolerance, we generated genetically manipulated (GM) chickens by retroviral gene transduction, to produce a fusion protein of chicken egg white lysozyme and a peptide derived from seven dominant human T-cell epitopes of Japanese cedar pollen allergens (cLys-7crp). The transgene sequence was detected in all chickens transduced with the retroviral vector. Transduction efficiency in blood cells correlated to transgene expression. Western blot analysis revealed that cLys-7crp was expressed in the egg white of GM hens. Mice induced to develop allergic rhinitis by Cj pollinosis were fed with cLys-7crp-containing egg white produced by GM chickens. Total and Cj allergen (Cry j 1)-specific IgE levels were significantly decreased in allergic mice fed with cLys-7crp-containing egg white compared with allergic mice fed with normal egg white. These results suggest that oral administration of T-cell epitope-containing egg white derived from GM chickens is effective for the induction of immune tolerance as an allergy therapy.
使用T细胞表位的肽免疫疗法有望成为治疗诸如日本柳杉花粉症等过敏性疾病的有效方法。为了通过诱导口服耐受来开发一种治疗花粉过敏的方法,我们通过逆转录病毒基因转导产生了基因改造(GM)鸡,以生产鸡蛋清溶菌酶与源自日本柳杉花粉过敏原七个主要人类T细胞表位的肽的融合蛋白(cLys-7crp)。在所有用逆转录病毒载体转导的鸡中均检测到转基因序列。血细胞中的转导效率与转基因表达相关。蛋白质印迹分析表明,cLys-7crp在转基因母鸡的蛋清中表达。用转基因鸡生产的含cLys-7crp的蛋清喂养因日本柳杉花粉症诱发过敏性鼻炎的小鼠。与用正常蛋清喂养的过敏小鼠相比,用含cLys-7crp的蛋清喂养的过敏小鼠的总IgE水平和日本柳杉过敏原(Cry j 1)特异性IgE水平均显著降低。这些结果表明,口服源自转基因鸡的含T细胞表位的蛋清作为一种过敏疗法,对于诱导免疫耐受是有效的。