In clinical therapy,the amount of antigen administered to achieve oral tolerance for allergic diseases is large,and the cost is a major consideration.In this study,we used tobacco plants to develop a large-scale prote...In clinical therapy,the amount of antigen administered to achieve oral tolerance for allergic diseases is large,and the cost is a major consideration.In this study,we used tobacco plants to develop a large-scale protein production system for allergen-specific immunotherapy,and we investigated the mechanisms of oral tolerance induced by a transgenic plant-derived antigen.We used plants(tobacco leaves)transgenic for the Dermatophagoides pteronyssinus 2(Der p2)antigen to produce Der p2.Mice received total protein extract from Der p2 orally once per day over 6 days(days 0–2 and days 6–8).Mice were also sensitized and challenged with yeast-derived recombinant Der p2(rDer p2),after which the mice were examined for airway hyper-responsiveness and airway inflammation.After sensitization and challenge with rDer p2,mice that were fed with total protein extracted from transgenic plants showed decreases in serum Der p2-specific IgE and IgG1 titers,decreased IL-5 and eotaxin levels in bronchial alveolar lavage fluid,and eosinophil infiltration in the airway.In addition,hyper-responsiveness was also decreased in mice that were fed with total protein extracted from transgenic plants,and CD4^(+)CD25^(+)Foxp3^(+) regulatory T cells were significantly increased in mediastinal and mesenteric lymph nodes.Furthermore,splenocytes isolated from transgenic plant protein-fed mice exhibited decreased proliferation and increased IL-10 secretion after stimulation with rDer p2.The data here suggest that allergen-expressing transgenic plants could be used for therapeutic purposes for allergic diseases.展开更多
文摘In clinical therapy,the amount of antigen administered to achieve oral tolerance for allergic diseases is large,and the cost is a major consideration.In this study,we used tobacco plants to develop a large-scale protein production system for allergen-specific immunotherapy,and we investigated the mechanisms of oral tolerance induced by a transgenic plant-derived antigen.We used plants(tobacco leaves)transgenic for the Dermatophagoides pteronyssinus 2(Der p2)antigen to produce Der p2.Mice received total protein extract from Der p2 orally once per day over 6 days(days 0–2 and days 6–8).Mice were also sensitized and challenged with yeast-derived recombinant Der p2(rDer p2),after which the mice were examined for airway hyper-responsiveness and airway inflammation.After sensitization and challenge with rDer p2,mice that were fed with total protein extracted from transgenic plants showed decreases in serum Der p2-specific IgE and IgG1 titers,decreased IL-5 and eotaxin levels in bronchial alveolar lavage fluid,and eosinophil infiltration in the airway.In addition,hyper-responsiveness was also decreased in mice that were fed with total protein extracted from transgenic plants,and CD4^(+)CD25^(+)Foxp3^(+) regulatory T cells were significantly increased in mediastinal and mesenteric lymph nodes.Furthermore,splenocytes isolated from transgenic plant protein-fed mice exhibited decreased proliferation and increased IL-10 secretion after stimulation with rDer p2.The data here suggest that allergen-expressing transgenic plants could be used for therapeutic purposes for allergic diseases.