Enhanced cytolytic activity of intestinal intraepithelial lymphocytes in patients with Crohn's disease

Background and aims: Dysfunction of the immune system with inappropriate re sponses of lymphocytes to various antigens has been implicated in the devel opment of Crohn's disease. Therefore, the functional and phenotypic charact eristics of intestinal intraepithelial lymphocytes (IEL) in comparison to p eripheral blood lymphocytes (PBL) were analyzed in patients with and withou t Crohn's disease. Patients and methods: Six patients with Crohn's disease and six control patients were studied. Isolated IEL and PBL were tested for cytolytic activity against the human adenocarcinoma cells DLD-1 and the hu man leukemia cells K562 in a Cr-51-release assay. Two-color now cytometry w as performed for phenotype analysis of isolated lymphocytes. Results: IEL f rom patients with Crohn's disease showed significantly increased cytolytic activity against epithelial-derived target cells when compared with IEL fro m control patients. In contrast, no Functional changes were detectable amon g PBL from patients with Crohn's disease. IEL from patients with Crohn's di sease contained a significantly higher percentage of CD8(+) lymphocytes whe n compared with IEL from control patients, whereas no phenotypic changes we re observed among PBL. Conclusions: In Crohn's disease, the functional and phenotypic changes of T cells arc, limited to lymphocytes of the intestinal mucosa. Furthermore, it is conceivable that the increased cytolytic activi ty of IEL contributes to the tissue damage in this disease.