Food antigen causes TH2-dependent enteropathy followed by tissue repair in T-cell receptor transgenic mice.
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.


CONCLUSIONS
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.


CONCLUSIONS
Long-term antigen intake causes T(H)2-dependent and food-sensitive enteropathy followed by tissue repair.
Nakajima-Adachi
Haruyo
H
Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, University of Tokyo, Yayoi, Japan. aryu@mail.ecc.u-tokyo.ac.jp
Ebihara
Ayumi
A
Kikuchi
Akira
A
Ishida
Tsuyoshi
T
Sasaki
Kiyomi
K
Hirano
Kiyomi
K
Watanabe
Hiroko
H
Asai
Kazumi
K
Takahashi
Yoshimasa
Y
Kanamori
Yutaka
Y
Shimojo
Naoki
N
Matsuda
Hiroshi
H
Kohno
Yoichi
Y
Hachimura
Satoshi
S
Kaminogawa
Shuichi
S