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

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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 IFN gamma 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 migh lead to mucosal destruction and crypt hyperplasia as seen in pouchitis.

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