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PMID: 11254669 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Th1-type responses mediate spontaneous ileitis in a novel murine model of Crohn's disease.

The Journal of clinical investigation ·Vol. 107 ·No. 6 ·2001-03-00 ·Pages 695-702

Kosiewicz MM, Nast CC, Krishnan A, Rivera-Nieves J, Moskaluk CA, Matsumoto S, Kozaiwa K, Cominelli F

Abstract

We describe here the immunologic characterization of a new mouse strain, SAMP1/Yit, which spontaneously develops a chronic intestinal inflammation localized to the terminal ileum. The resulting ileitis bears a remarkable resemblance to human Crohn's disease. This strain of mice develops discontinuous, transmural inflammatory lesions in the terminal ileum with 100% penetrance by 30 weeks of age. The intestinal inflammation is characterized by massive infiltration of activated CD4+ and CD8alpha(+)TCRalphabeta(+) T cells into the lamina propria and is accompanied by a dramatic decrease in the intraepithelial lymphocyte CD8alpha(+)TCRgammadelta(+)/CD8alpha(+)TCRalphabeta(+) ratio. The results of adoptive transfer experiments strongly suggest that CD4+ T cells that produce a Th1-like profile of cytokines, e.g., IFN-gamma and TNF, mediate the intestinal inflammation found in SAMP1/Yit mice. In addition, pretreatment of adoptive transfer recipients with a neutralizing anti-TNF antibody prevents the development of intestinal inflammation, suggesting that TNF plays an important role in the pathogenesis of intestinal inflammation in this model. To our knowledge, these data provide the first direct evidence that Th1-producing T cells mediate intestinal inflammation in a spontaneous animal model of human Crohn's disease.

MeSH Terms
Adoptive Transfer Animals Crohn Disease/etiology Cytokines/biosynthesis Disease Models, Animal Female Humans Ileitis/etiology,immunology,pathology Mice Mice, Inbred AKR Mice, Inbred Strains Mice, SCID Neutralization Tests Th1 Cells/immunology Tumor Necrosis Factor-alpha/antagonists & inhibitors,immunology
Chemicals
Cytokines Tumor Necrosis Factor-alpha
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Kosiewicz M M
Departments of Medicine and Pathology, University of Virginia Health System, Charlottesville, Virginia 22908, USA.
Nast C C
Krishnan A
Rivera-Nieves J
Moskaluk C A
Matsumoto S
Kozaiwa K
Cominelli F
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI10956
Published
2001-03-00
Pages
695-702
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC208944
Subset
IM
Grants
NIDDK NIH HHS · K08 DK067254 · United States
NIDDK NIH HHS · DK-42191 · United States
NIDDK NIH HHS · DK-55812 · United States
NIDDK NIH HHS · R37 DK042191 · United States
NIDDK NIH HHS · R56 DK042191 · United States
NIDDK NIH HHS · R01 DK042191 · United States
NIDDK NIH HHS · P01 DK057880 · United States
NIDDK NIH HHS · DK-57880 · United States
NIDDK NIH HHS · R01 DK055812 · United States
Corrections
CommentIn
PMID: 11254665
External Links
PubMed source DOI: 10.1172/JCI10956 PMC Full Text View journal details
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