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. 2001 Jul;49(1):35-41.
doi: 10.1136/gut.49.1.35.

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

J Itoh  1 , C de La Motte, S A Strong, A D Levine, C Fiocchi
Affiliations

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

J Itoh et al. Gut. 2001 Jul.

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-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.

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Figures

Figure 1
Figure 1
Representative flow cytometric analysis of intracellular staining for Bcl-2, Bcl-xL, and Bax protein levels in normal peripheral blood T cells (PBT) and control lamina propria T cells (LPT).
Figure 2
Figure 2
Flow cytometric analysis of intracellular staining for Bcl-2, Bcl-xL, and Bax protein levels in normal peripheral blood T cells (PBT) and control lamina propria T cells (LPT). Results are mean (SEM) fluorescence intensity for eight PBT and 10 LPT isolates. **p<0.002, ***p<0.001.
Figure 3
Figure 3
Flow cytometric analysis of intracellular staining for Bcl-2, Bcl-xL, and Bax protein levels in normal unseparated and CD45RO enriched (+) peripheral blood T cells (PBT). Results are mean (SEM) fluorescence intensity for eight PBT isolates. No statistically significant differences were observed for Bcl-2, Bcl-xL, and Bax.
Figure 4
Figure 4
Correlation of anti- and proapoptotic Bcl-2 family protein levels in normal peripheral blood T cells (PBT) (top) and control lamina propria T cells (LPT) (bottom). Individual data points represent mean fluorescence intensity of intracellular staining measured by flow cytometric analysis.
Figure 5
Figure 5
Representative flow cytometric analysis of intracellular staining for Bcl-2, Bcl-xL, and Bax protein levels in control, Crohn's disease (CD) and ulcerative colitis (UC) lamina propria T cells (LPT).
Figure 6
Figure 6
Flow cytometric analysis of intracellular staining for Bcl-2, Bcl-xL, and Bax protein levels in control, Crohn's disease (CD), and ulcerative colitis (UC) lamina propria T cells (LPT). Results are mean (SEM) fluorescence intensity for 10 control, seven CD, and eight UC isolates. **p<0.003, CD versus control and UC.
Figure 7
Figure 7
Correlation of proapoptotic Bax and antiapoptotic Bcl-xL protein levels in Crohn's disease (CD) and ulcerative colitis (UC) lamina propria T cells (LPT). Individual data points represent mean fluorescence intensity of intracellular staining measured by flow cytometric analysis.
Figure 8
Figure 8
Comparative correlation of proapoptotic Bax and antiapoptotic Bcl-xL in control and Crohn's disease (CD) lamina propria T cells (LPT). Individual data points represent mean fluorescence intensity of intracellular staining measured by flow cytometric analysis.
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Comment in

  • Surviving too long in Crohn's disease.
    Di Sabatino A, Corazza GR. Di Sabatino A, et al. Gut. 2001 Jul;49(1):6-8. doi: 10.1136/gut.49.1.6. Gut. 2001. PMID: 11413101 Free PMC article. No abstract available.

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