Food antigen causes T_H2-dependent enteropathy followed by tissue repair in T-cell receptor transgenic mice - 17/08/11

Doi : 10.1016/j.jaci.2006.01.016

Haruyo Nakajima-Adachi, PhD ^a,^⁎ , Ayumi Ebihara, MS ^a, Akira Kikuchi, MS ^a, Tsuyoshi Ishida, MD ^b, Kiyomi Sasaki, BS ^a, Kiyomi Hirano ^c, Hiroko Watanabe, PhD ^d, Kazumi Asai, PhD ^a, Yoshimasa Takahashi, PhD ^e, Yutaka Kanamori, MD ^f, Naoki Shimojo, MD, PhD ^c, Hiroshi Matsuda, DVM, PhD ^g, Yoichi Kohno, MD, PhD ^c, Satoshi Hachimura, PhD ^a, Shuichi Kaminogawa, PhD ^h
^a From the Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, University of Tokyo
^b Department of Diagnostic Pathology, Kanto Medical Center Nippon Telegraph and Telephone East Corporation, Tokyo
^c Department of Pediatrics, Chiba University
^d Chemistry Division, Kanagawa Prefectural Institute of Public Health
^e Department of Immunology, National Institute of Infectious Diseases, Tokyo
^f Department of Pediatric Surgery, University of Tokyo
^g Division of Animal Science, Graduate School, Institute of Symbiotic Science and Technology, Tokyo University of Agriculture and Technology
^h Department of Food Science and Technology, Nihon University College of Bioresource Sciences, Kanagawa

Reprint requests: Haruyo Nakajima-Adachi, PhD, Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-Ku, Tokyo 113-8657, Japan.

Tokyo, Chiba, and Kanagawa, Japan

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_H2 responses play important roles in regulation of development and improvement of the disease.

Clinical implications

Long-term antigen intake causes T_H2-dependent and food-sensitive enteropathy followed by tissue repair.

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Key words : T-cell receptor transgenic mouse, food-sensitive intestinal inflammation, ovalbumin, food antigen intake, antigen-specific T cells, IgE, mast cell, T_H2, histamine, tissue repair

Abbreviations used : AB, BALB-mice, CN, CNB, DFS, EW, EWB, EWR, FITC, MLN, OVA, PAS, TB, TCR, Tg-mice