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

We describe here the immunologic characterization of a new mouse strain, SA MP1/Yit, which spontaneously develops a chronic intestinal inflammation loc alized to the terminal ileum. The resulting ileitis bears a remarkable rese mblance to human Crohn's disease. This strain of mice develops discontinuou s, transmural inflammatory lesions in the terminal ileum with 100% penetran ce by 30 weeks of age. The intestinal inflammation is characterized by mass ive infiltration of activated CD4(+) and CD8 alpha +TCR alpha beta (+) T ce lls into the lamina propria and is accompanied by a dramatic decrease in th e 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 infla mmation, suggesting that TNF plays an important role in the pathogenesis of intestinal inflammation in this model. To our knowledge, these data provid e the first direct evidence that Th1-producing T cells mediate intestinal i nflammation in a spontaneous animal model of human Crohn's disease.