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  • Title: Food antigen causes TH2-dependent enteropathy followed by tissue repair in T-cell receptor transgenic mice.
    Author: Nakajima-Adachi H, Ebihara A, Kikuchi A, Ishida T, Sasaki K, Hirano K, Watanabe H, Asai K, Takahashi Y, Kanamori Y, Shimojo N, Matsuda H, Kohno Y, Hachimura S, Kaminogawa S.
    Journal: J Allergy Clin Immunol; 2006 May; 117(5):1125-32. PubMed ID: 16675342.
    Abstract:
    BACKGROUND: Clarification of the mechanisms underlying the development of food-sensitive intestinal inflammation will provide an important clue to combating food allergies. OBJECTIVE: To establish a model of intestinal inflammation caused by oral administration of antigen without additional treatments, we focused on the ovalbumin (OVA) 23-3 T-cell receptor transgenic mouse, which had been reported to have high serum antigen-specific IgE responses to the feeding of an egg white diet. METHODS: Changes in body weight of mice fed an egg white diet were monitored throughout the 28-day experimental period. After the 28-day feeding, intestinal tissues were harvested for histologic examination. Endogenous production of cytokines and histamine in the jejunum, and production of cytokines secreted by OVA-specific CD4+ T cells purified from mesenteric lymph nodes, were analyzed. RESULTS: Egg white diet-fed OVA23-3 mice developed weight loss and inflammation with villous atrophy and goblet cell hyperplasia, especially in the jejunum. A further characteristic feature was evidence of weight recovery and tissue repair. Jejunal inflammation was also observed in egg white diet-fed recombination activating gene (RAG)-2-deficient OVA23-3 mice. In addition, tissue sections revealed significant infiltration of specific IgE-positive cells and IgE-positive degranulating mast cells. Higher levels of IL-4 and significant levels of histamine were detected in the tissues. In the supernatant of OVA-stimulated T cells, IL-10 levels were also markedly elevated. CONCLUSION: We report that high-dose and continuous intake of primitive OVA alone induces enteropathy containing regions under repair in OVA23-3 mice. Antigen-specific T cells and inflammatory cells primed by T(H)2 responses play important roles in regulation of development and improvement of the disease. CLINICAL IMPLICATIONS: Long-term antigen intake causes T(H)2-dependent and food-sensitive enteropathy followed by tissue repair.
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