Th1-type responses mediate spontaneous ileitis in a novel murine model of Crohn's disease
Th1-type responses mediate spontaneous ileitis in a novel murine model of Crohn's disease
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DOI：
10.1172/jci10956
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发表时间：
2001-03-01
影响因子：
15.9
通讯作者：
Cominelli, F
中科院分区：
文献类型：
--
作者：
Kosiewicz, MM;Nast, CC;Cominelli, F
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 CD8 alpha +TCR alpha beta (+) T cells into the lamina propria and is accompanied by a dramatic decrease in the intraepithelial lymphocyte CD8 alpha +TCR gamma delta (+)/CD8 alpha +TCR alpha beta (+) ratio. The results of adoptive transfer experiments strongly suggest that CD4(+) T cells that produce a Th1-Like profile of cyokines, 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.
