Abstract
Intraepithelial lymphocytes (IEL) of the small murine bowel represent a unique population of mostly CD8+ T lymphocytes that reside within the epithelial cell layer of the intestinal mucosa. The close interaction with epithelial cells appears to be crucial for IEL survival since isolation and ex vivo culture induces massive apoptosis in this lymphocyte population. Here, we provide evidence that this form of IEL cell death may be mediated at least in part by endogenously produced glucocorticoids since adrenalectomy or treatment of mice with a glucocorticoid receptor antagonist significantly enhanced ex vivo survival of IEL. We further demonstrate that ex vivo activation of IEL induces upregulation of anti-apoptotic gene products, compensates for the lack of survival cytokines and rescues from apoptotic cell death. Thus, similar to thymocytes and T cell hybridomas, IEL survival may be regulated by the antagonistic action of TCR activation and glucocorticoids.
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Abbreviations
- AICD:
-
activation-induced cell death
- CD95:
-
Fas/APO-1
- CD95L:
-
CD95 ligand
- sCD95-Fc:
-
soluble CD95-human IgG1 fusion protein
- cIAP:
-
cellular inhibitor of apoptosis
- dex:
-
dexamethasone
- HBS:
-
HEPES-buffered saline
- IL:
-
interleukin
- IEL:
-
intraepithelial lymphocytes
- PMA:
-
phorbolmyristate acetate
- RT–PCR:
-
reverse transcription polymerase chain reaction
- RU-486:
-
mifepristone
- TGFβ:
-
transforming growth factor β
- TCR:
-
T cell receptor
- TNFα:
-
tumor necrosis factor α
- TUNEL:
-
TdT-mediated dUTP nick end labeling
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Acknowledgements
The authors would like to thank C Mueller, SJ Martin, and B Cenni for helpful discussion, precious advice on experiments and the manuscript, C Vallan for help with flow cytometry, N Corazza, S Müller, I Vogt, C Frey and M Bühler-Jungo for technical help and advice on the experiments, C Murtin for help with the RT–PCR, R Sitruk-Ware for providing RU-486, DR Green and A Mahboubi for sCD95-Fc, SJ Martin for antibodies, JA Laissue, K Brunetta Brunner and F Brunner for support. This work was supported by grants from the Swiss National Science Foundation (31-54079.98) and Swiss Cancer League (SKL 617-2-98) to T Brunner.
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Brunner, T., Arnold, D., Wasem, C. et al. Regulation of cell death and survival in intestinal intraepithelial lymphocytes. Cell Death Differ 8, 706–714 (2001). https://doi.org/10.1038/sj.cdd.4400854
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DOI: https://doi.org/10.1038/sj.cdd.4400854
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