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Decreased Bax expression by mucosal T cells favours resistance to apoptosis in Crohn's disease

2001; BMJ; Volume: 49; Issue: 1 Linguagem: Inglês

10.1136/gut.49.1.35

1468-3288

Jugoh Itoh,

Inflammatory Bowel Disease

BACKGROUND Activated T cells are more susceptible to apoptosis than resting T cells. As intestinal T cells normally exhibit a higher state of activation, increased apoptosis may be necessary to maintain immune homeostasis in the specialised microenvironment of the mucosa. On the other hand, in Crohn9s disease (CD) mucosal T cells are resistant to apoptosis, suggesting abnormal regulation of cell death mechanisms. AIMS To investigate differences in expression of anti- and proapoptotic Bcl-2 family proteins, key regulators of apoptosis, between circulating and mucosal T cells, and possible alterations in CD. PATIENTS AND METHODS Lamina propria T cells (LPT) were isolated from 10 control, seven CD, and eight ulcerative colitis (UC) patients, and peripheral blood T cells (PBT) from healthy volunteers. Purified T cells were stained intracellularly for Bcl-2, Bcl-x L , and Bax, and mean fluorescence intensity measured by flow cytometry. RESULTS Compared with PBT, the expression level of Bcl-2 and Bax, but not Bcl-x L , was significantly greater in LPT, resulting in lower Bcl-x L /Bax ratios. In PBT, Bax expression was highly and significantly correlated with both Bcl-2 and Bcl-x L , but correlation with Bcl-2 was absent in LPT. Bax expression in CD, but not UC, LPT was significantly lower than in control LPT, resulting in a significantly higher Bcl-x L /Bax ratio. The significant correlation of Bcl-x L to Bax was preserved in CD, but not UC, LPT. CONCLUSIONS Regulation of Bcl-2 family protein expression differs between circulating and mucosal T cells, probably underlying diverse survival potentials. In CD LPT, a low Bax expression and a high Bcl-x L /Bax ratio favour resistance to apoptosis and may contribute to the chronicity of inflammation.