Study on oral Tolerance Induced by Short-term Feeding of Dp2 Protein to Mice sensitized and Challenged with Dp2 Protein

• Main Authors: Ming-Chih Hsu, 許銘志
• Other Authors: 林璧鳳
• Format: Others
• Language: zh-TW
• Published: 2007
• Online Access: http://ndltd.ncl.edu.tw/handle/49667110591989068427

碩士 === 國立臺灣大學 === 微生物與生化學研究所 === 95 === The dust mite is a major allergen for allergic asthma, an airway chronic inflammatory disease. About 80 ~ 90% of patients who react to mite extract react specifically to dust mite protein group 2, Dp2. Oral tolerance is a state of immunological unresponsiveness to allergen induced by feeding. Our previous study demonstrated that oral tolerance was induced efficiently by continuous feeding of Dp2 for seven days. Therefore, to investigate mechanisms of oral tolerance used in asthma, the mRNA expression and immune response in the process of oral tolerance induction, three trials including a short-term oral administration of Dp2, an added three intra-peritoneal (IP) boosting and an extra intra-tracheal (IT) challenge, were conducted. In the short-term feeding trial, the tolerance group significantly enhanced mRNA expressions of CRIP3, CD226 and Foxp3 in Peyer’s patch (PP) and Dp2-stimulated IFN-g secretion from splenocytes, indicating a Th1 dominant immunomodulation by oral induction. Although CD226 became lower in oral tolerance group after IP boosting and IT challenge, Foxp3, a transcriptional factor in regulatory T cell, remained significantly higher during the sensitization process. The CD4+CD25+ level, a regulatory T cell marker, in splenocytes and PP were also significantly higher suggesting that regulatory immune cells were induced and differentiation of splenocytes might be affected by oral tolerance. Therefore, IL-4 and IL-5 secretion were suppressed, and TGF-b1 secretion was increased in oral tolerance group during the following sensitization. The Dp2-stimulated proliferation of splenocyte and serum total IgE level decreased significantly in oral tolerance group after IP boosting. Airway hypersensitivity, Th2 cytokine such as IL-4 and IL-13 in BALF, both serum total IgE and Dp2-specific IgE levels significantly decreased in the tolerance group after IT challenge. In summary, short-term oral administration of Dp2 altered long term intestinal gene expression such as Foxp3, and induced more regulatory T cells and suppressed allergic immune responses to achieve the long-term tolerance outcome.