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

Abstract

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 Crohn's 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-xL, and Bax, and mean fluorescence intensity measured by flow cytomerry. Results - Compared with PBT, the expression level of Bcl-2 and Bax, but not Bcl-xL, was significantly greater in LPT, resulting in lower Bcl-xL/Bax ratios. In PBT, Bax expression was highly and significantly correlated with both Bcl-2 and Bcl-xL, 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-xL/Bax ratio. The significant correlation of Bcl-xL to Bax was preserved in CD, but not UC, LPT. Conclusions - Regulation of Bc1-2 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-xLBax ratio favour resistance to apoptosis and may contribute to the chronicity of inflammation.