Oral administration of food antigen induces T cell mediated intestinal inflammation: a model using TCR-transgenic mice.
To investigate the mechanisms inducing food-sensitive intestinal inflammation, we focused on the OVA23-3 mouse, a transgenic mouse strain expressing a T cell receptor that recognizes ovalbumin (OVA). Mice administered an egg-white (EW) diet containing OVA showed a trend of loose feces and significant weight loss. Histology of the jejunum showed severe inflammation with villous atrophy. Thus, we studied the role of T cells and intestinal microflora in the development of the inflammation. Severe villous disruption was observed in sections of the jejunum from OVA23-3 mice and RAG-2 gene-deficient OVA23-3 mice fed with EW-diet. Further, a larger number of T cells was found in the lamina propria of the jejunum of EW-diet fed OVA23-3 mice, RAG-2 gene-deficient mice and germfree OVA23-3 mice compared with those of control-diet fed mice. However, severe inflammation was not detected in the jejunum of germfree OVA23-3 mice. CD4+ T cells from the MLN of EW-diet fed OVA23-3 mice showed a Th2 cytokine secretion profile. These observations have thus clarified that antigen-specific Th2 cells play important roles in the development of intestinal inflammation. Although the presence of indigenous bacteria was not essential for the inflammation, T cells could mediate a more severe inflammatory response in their presence.
Kikuchi
Akira
A
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.
Nakajima-Adachi
Haruyo
H
Ebihara
Ayumi
A
Takahashi
Yoshimasa
Y
Hosono
Akira
A
Itoh
Kikuji
K
Hachimura
Satoshi
S
Kaminogawa
Shuichi
S
D000818:Animals; D000941:Antigens / Q000276:immunology*; D004195:Disease Models, Animal; D005502:Food / Q000009:adverse effects*; D005856:Germ-Free Life; D018928:Immunity, Mucosal; D007249:Inflammation / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology* / Q000469:parasitology; D007583:Jejunum / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000009:adverse effects; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D015431:Weight Loss
D000941:Antigens; D011948:Receptors, Antigen, T-Cell; D010047:Ovalbumin