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PMID: 15466391 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

CD4+CD45RBHi interleukin-4 defective T cells elicit antral gastritis and duodenitis.

The American journal of pathology ·Vol. 165 ·No. 4 ·2004-10-00 ·Pages 1257-68

Dohi T, Fujihashi K, Koga T, Etani Y, Yoshino N, Kawamura YI, McGhee JR

Abstract

We have analyzed the gastrointestinal inflammation which develops following adoptive transfer of IL-4 gene knockout (IL-4(-/-)) CD4(+)CD45RB(Hi) (RB(Hi)) T cells to severe combined immunodeficient (SCID) or to T cell-deficient, T cell receptor beta and delta double knockout (TCR(-/-)) mice. Transfer of IL-4(-/-) RB(Hi) T cells induced a similar type of colitis to that seen in SCID or TCR(-/-) recipients of wild-type (wt) RB(Hi) T cells as reported previously. Interestingly, transfer of both wt and IL-4(-/-) RB(Hi) T cells to TCR(-/-) but not to SCID mice induced inflammation in the gastric mucosa. Notably, TCR(-/-) recipients of IL-4(-/-) RB(Hi) T cells developed a more severe gastritis with erosion, apoptosis of the antral epithelium, and massive infiltration of macrophages. This gastritis was partially dependent on the indigenous microflora. Recipients of both wt and IL-4(-/-) RB(Hi) T cells developed duodenitis with multinuclear giant cells, expansion of mucosal macrophages, and dendritic cells. Full B cell responses were reconstituted in TCR(-/-) recipients of RB(Hi) T cells; however, anti-gastric autoantibodies were not detected. We have now developed and characterized a novel model of chronic gastroduodenitis in mice, which will help in our understanding of the mechanisms involved in chronic inflammation in the upper gastrointestinal tract of humans.

MeSH Terms
Adoptive Transfer Animals Arabidopsis Proteins B-Lymphocytes/immunology CD4 Antigens CD4-Positive T-Lymphocytes/immunology Cytokines/analysis Disease Models, Animal Duodenitis/immunology,pathology Gastritis/immunology,pathology Interleukin-4/deficiency Intestinal Mucosa/immunology Leukocyte Common Antigens Mice Mice, Knockout Mice, SCID Pyloric Antrum/immunology,pathology RNA, Messenger/analysis Receptors, Antigen, T-Cell/deficiency Reverse Transcriptase Polymerase Chain Reaction T-Lymphocyte Subsets/immunology
Chemicals
Arabidopsis Proteins CD4 Antigens Cytokines PCC1 protein, Arabidopsis RNA, Messenger Receptors, Antigen, T-Cell Interleukin-4 Leukocyte Common Antigens
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Dohi Taeko
Department of Gastroenterology, Research Institute, International Medical Center of Japan, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan. [email protected].
Fujihashi Kohtaro
Koga Toshiya
Etani Yuri
Yoshino Naoto
Kawamura Yuki I
McGhee Jerry R
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Article Info
Journal
The American journal of pathology
Abbr.
Am J Pathol
ISSN
0002-9440
DOI
10.1016/S0002-9440(10)63385-8
Email
[email protected]
Published
2004-10-00
Pages
1257-68
Language
English
Region
United States
NLM ID
0370502
PMCID
PMC1618629
Subset
IM
Grants
NIAID NIH HHS · AI 43197 · United States
NIDDK NIH HHS · DK 44240 · United States
NIDCR NIH HHS · R01 DE012242 · United States
NIAID NIH HHS · R01 AI018958 · United States
NIDCD NIH HHS · R01 DC004976 · United States
NIDCR NIH HHS · R29 DE012242 · United States
NIAID NIH HHS · AI 35932 · United States
NIAID NIH HHS · AI 18958 · United States
NIDCR NIH HHS · DE 12242 · United States
NIDDK NIH HHS · P01 DK044240 · United States
NIDCD NIH HHS · DC 04976 · United States
NIAID NIH HHS · R01 AI043197 · United States
External Links
PubMed source DOI: 10.1016/S0002-9440(10)63385-8 PMC Full Text View journal details
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