Induction of antigen-specific tolerance by oral administration of Der p 2 allergen in a murine model of asthma

• Main Authors: Fan-Chi Hsu, 徐凡祺
• Other Authors: 江伯倫
• Format: Others
• Language: en_US
• Published: 2005
• Online Access: http://ndltd.ncl.edu.tw/handle/00267171606959850095

碩士 === 國立臺灣大學 === 口腔生物科學研究所 === 93 === Abstract Asthma is one of the most common allergic diseases in children, and affects more than 10% children population in both developing and developed countries. Allergic asthma is associated with airway hyperresponsiveness (AHR), eosinophils infiltration and increased mucus secretion in the airway. Oral administration of antigen is a method of inducing antigen-specific unresponsiveness that is called oral tolerance. That is result of inducing antigen-specific T cells anergy or deletion or a group of antigen-specific regulatory T cells to suppress antigen-specific immune response. The induction of oral tolerance is suggested to be a possible immunotherapy for allergic diseases. A large amount of allergen is needed for oral administration to induce oral tolerance. However, the traditional method to generate a specific allergen from natural mites, plant or animal extracts is limited due to the problem of other unnecessary molecules contamination and expensive but low-yield production. Recombinant technologies can be used to prevent these problems. We hope to develop a large scale protein expression system for allergen specific immunotherapy. In the present study, we used the yeast Pichia pastoris protein expression systems for producing the major allergen, house dust mite Dermatophagoides pteronyssinus group 2 allergen (Der p 2). Then, the recombinant Der p 2 proteins derived from yeast was fed to a Der p 2-sensitized asthma murine model to investigate the application of oral tolerance induction as therapy for allergic asthma. Furthermore, we also generated a protein expression system of Der p 2-transgenic tomato plant to produce large amount of rDer p 2. In this study, oral feeding with low dose of rDer p 2 derived from yeast would decrease Der p 2-specific IgE and IgG1 titers in serum after immunization. The airway hyperresponsiveness was significantly reduced in mice fed with rDer p 2 compared to the positive control. The infiltration of eosinophils in BALF was also decreased in mice fed with rDer p 2. Those results indicated that mice fed with rDer p 2 could inhibit the local airway inflammation. However, the systemic immunological tolerance indexes, such as the proliferation and cytokine secretion upon allergen stimulation of splenocytes, did not show significant difference. Conclusively, our data suggested that oral delivery of low dose yeast-derived rDer p 2 could induce oral tolerance in a local allergic airway inflammation murine model. The application of oral delivery of Der p 2-transgenic tomato to induce oral tolerance as a new therapy for asthma diseases is prospective.