Increased proportion of CD16(+) NK cells in the colonic lamina propria of inflammatory bowel disease patients, but not after azathioprine treatment.

BACKGROUND: Distinct functional subsets of natural killer cells potentially contribute to the pathology of inflammatory bowel disease (IBD). AIM: To report the phenotypic and functional characteristics of natural killer cells in blood and lamina propria of IBD patients, and the effect of azathioprine. METHODS: Natural killer cells from blood and lamina propria of healthy controls or patients with Crohn's disease, or ulcerative colitis were studied by flow cytometry. Activation, cytokine production, proliferation and apoptosis of natural killer cell subsets were studied in vitro. RESULTS: CD16(+) natural killer cells are increased in frequency in the lamina propria comparing Crohn's disease or ulcerative colitis with healthy controls. Azathioprine therapy was associated with a reduction in total natural killer cells in blood and lamina propria, preferentially of the CD16(+) subset. Azathioprine therapy did not impair natural killer degranulation, but reduced natural and cytokine-activated cytotoxicity and interferon-gamma (IFN-γ) production. Culture of resting peripheral blood mononuclear cells with azathioprine resulted in loss of natural killer cells and inhibition of activation and IFN-γ production. Azathioprine preferentially inhibited proliferation of CD16(+) natural killer cells and induced apoptosis in resting but not in pre-activated natural killer cells. CONCLUSIONS: Natural killer cells with cytolytic potential are enriched in the colonic lamina propria of individuals with IBD. Azathioprine is associated with a reduction in these cells and a normalization of natural killer cell populations.