Increased state of activation of CD4 positive T cells and elevated interferon γ production in pouchitis

Abstract

BACKGROUND: Immunoregulatory abnormalities of T cells might be of importance in the pathogenesis of pouchitis after ileoanal pouch anastomosis (IAP). AIMS: To characterise T cell subsets, their state of activation, and production of cytokines in inflamed and non-inflamed pouches in patients with ulcerative colitis (UC) and familial adenomatous polyposis (FAP). The influence of T cell activation on mucosal transformation was also studied. PATIENTS: Mucosal biopsy specimens were taken from 42 patients with IAP (33 with UC and nine with FAP). METHODS: Mononuclear cells were isolated by standard techniques and characterised by three colour flow cytometry. Interferon gamma (IFN-gamma) production was studied using the ELISPOT technique. RESULTS: In patients with UC with pouchitis there was a significant increase in the CD4:CD8 ratio, expression of activation markers on CD3+ cells, and number of IFNgamma producing mononuclear cells compared with patients with UC without pouchitis (CD4:CD8 ratio 1.3 (range 0.7-2.7) versus 0.6 (0. 1-1.0), p=0.012). In addition, a positive correlation between increased crypt depth and the number of CD4+ cells (r=0.57) was shown. CONCLUSION: The observed increase in activated mucosal CD4+ T cells and IFN-gamma production might lead to mucosal destruction and crypt hyperplasia as seen in pouchitis.