Transgenic plants expressing autoantigens fed to mice to induce oral immune tolerance
Transgenic plants expressing autoantigens fed to mice to induce oral immune tolerance
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DOI：
10.1038/nm0797-793
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发表时间：
1997-07-01
期刊：
影响因子：
82.9
通讯作者：
Jevnikar, AM
中科院分区：
文献类型：
--
作者：
Ma, SW;Zhao, DL;Jevnikar, AM
口服蛋白质可诱导抗原特异性免疫低反应(1)。然而，当传统系统不能产生足够数量的候选自身抗原用于临床研究时，口服耐受自身抗原在治疗自身免疫性疾病中的作用可能会受到限制。植物可能非常适合于这一目的，因为它们可以合成、糖基化和组装哺乳动物蛋白质，以提供大量相对低成本的可溶性蛋白质。此外，可食用的转基因植物可以为口服耐受提供一种简单直接的自身抗原传递方法。因此，本研究的目的是确定转基因植物表达系统是否能够以免疫原性的形式合成糖尿病相关自身抗原谷氨酸脱羧酶(GAD)(3，4)，以及口服植物表达的自身抗原是否能直接在糖尿病小鼠模型中诱导保护性免疫反应。我们发现，一种表达GAD的转基因植物，作为饮食补充剂，可以抑制非肥胖糖尿病(NOD)小鼠的糖尿病发展。
Oral administration of protein can induce antigen-specific immune hyporesponsiveness(1). However, the utility of oral tolerance to autoantigens in the treatment of autoimmune diseases may be limited when candidate autoantigens cannot be produced by conventional systems in quantities sufficient for clinical studies. Plants may be ideally suited for this purpose, as they can synthesize, glycosylate and assemble mammalian proteins to provide huge quantities of relatively low cost soluble proteins(2). Furthermore, edible transgenic plants could provide a simple and direct method of autoantigen delivery for oral tolerance. Therefore, the aim of this study was to determine whether a transgenic plant expression system was capable of synthesizing the diabetes-associated autoantigen, glutamic acid decarboxylase (GAD)(3,4) in an immunogenic form and whether the oral administration of an autoantigen expressed by a plant could directly induce protective immune responses in a mouse model of diabetes. We show that a GAD-expressing transgenic plant, given as a dietary supplement, inhibits the development of diabetes in the non-obese diabetic (NOD) mouse.