Kosiewicz M M, Nast C C, Krishnan A, Rivera-Nieves J, Moskaluk C A, Matsumoto S, Kozaiwa K, Cominelli F
Departments of Medicine and Pathology, University of Virginia Health System, Charlottesville, Virginia 22908, USA.
J Clin Invest. 2001 Mar;107(6):695-702. doi: 10.1172/JCI10956.
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.
我们在此描述一种新的小鼠品系SAMP1/Yit的免疫学特征，该品系会自发发生局限于回肠末端的慢性肠道炎症。由此产生的回肠炎与人类克罗恩病极为相似。这种小鼠品系在回肠末端会出现不连续的透壁性炎症病变，到30周龄时发病率达100%。肠道炎症的特征是活化的CD4+和CD8alpha(+)TCRalphabeta(+) T细胞大量浸润至固有层，并伴有上皮内淋巴细胞CD8alpha(+)TCRgammadelta(+)/CD8alpha(+)TCRalphabeta(+) 比值显著降低。过继转移实验结果强烈表明，产生Th1样细胞因子谱（如IFN-γ和TNF）的CD4+ T细胞介导了SAMP1/Yit小鼠的肠道炎症。此外，用过继转移受体用中和性抗TNF抗体进行预处理可预防肠道炎症的发生，这表明TNF在该模型的肠道炎症发病机制中起重要作用。据我们所知，这些数据首次直接证明了产生Th1的T细胞在人类克罗恩病的自发动物模型中介导肠道炎症。
