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

Abstract 

Background and aims: Dysfunction of the immune system with inappropriate responses of lymphocytes to various antigens has been implicated in the development of Crohn’s disease. Therefore, the functional and phenotypic characteristics of intestinal intraepithelial lymphocytes (IEL) in comparison to peripheral blood lymphocytes (PBL) were analyzed in patients with and without 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 human leukemia cells K562 in a ⁵¹Cr-release assay. Two-color flow cytometry was performed for phenotype analysis of isolated lymphocytes. Results: IEL from patients with Crohn’s disease showed significantly increased cytolytic activity against epithelial-derived target cells when compared with IEL from control patients. In contrast, no functional changes were detectable among PBL from patients with Crohn’s disease. IEL from patients with Crohn’s disease contained a significantly higher percentage of CD8⁺ lymphocytes when compared with IEL from control patients, whereas no phenotypic changes were observed among PBL. Conclusions: In Crohn’s disease, the functional and phenotypic changes of T cells are limited to lymphocytes of the intestinal mucosa. Furthermore, it is conceivable that the increased cytolytic activity of IEL contributes to the tissue damage in this disease.