Abstract
As it has been shown for Mcl-1, Bcl-xl and Bcl-2, proteins of the Bcl-2 family play a crucial role during T-cell development in the thymus. We here show that the expression of the antiapoptotic gene A1 is specifically enhanced at the DN3/DN4 transition and in DP thymocytes that have been positively selected suggesting that A1 expression might be considered as a transcriptional signature of thymocytes that have received pre-TCR or TCR survival signal. Furthermore, we observed that A1-a overexpression in recombination activation gene 1-deficient mice transgenic for the major histocompatibillity complex class I-restricted F5 TCR enhances cell survival of DP thymocytes and permits accumulation of DP cells awaiting positive selection. However, A1-a overexpression has no effect on negative selection. Therefore, our results suggest that A1 plays a specialized role in allowing survival of DP thymocytes and that its role can be distinguished from that of Mcl-1, Bcl-xl and Bcl-2.
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Abbreviations
- BrdU:
-
5–bromo-2′-deoxyuridine
- DP:
-
double positive
- DN:
-
double negative
- PBS:
-
phosphate buffer saline
- SP:
-
single positive
- TCR:
-
T-cell receptor
- Tg:
-
transgenic
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Acknowledgements
We would like to thank Dr Jacqueline Marvel for helpful discussions, Antoine Marçais for his help in adoptive transfer experiments and Dr. Janet Maryanski for critical reading of the manuscript. This work is supported by institutional grants from INSERM and UCB Lyon I, and additional support from the Association pour la Recherche sur le Cancer, The Ligue contre le cancer (comité du rhône), the Région Rhône-Alpes and Cancéropole National (NBB). C Verschelde is supported by a fellowship from The Association pour la Recherche sur le Cancer. I Berberich was supported by the Wilhem Sander-Stiftung (1999.107.2).
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Verschelde, C., Michonneau, D., Trescol-Biemont, MC. et al. Overexpression of the antiapoptotic protein A1 promotes the survival of double positive thymocytes awaiting positive selection. Cell Death Differ 13, 1213–1221 (2006). https://doi.org/10.1038/sj.cdd.4401814
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DOI: https://doi.org/10.1038/sj.cdd.4401814
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