Abstract
We analyzed regulation of the prosurvival Bcl-2 homologue A1, following T-cell receptor (TCR) or cytokine receptor engagement. Activation of CD4+ or CD8+ T cells by antigenic peptides induced an early but transient IL-2-independent expression of A1 and Bcl-xl mRNA and proteins, whereas expression of Bcl-2 was delayed and required IL-2. Cytokines such as IL-2, IL-4, IL-7 or IL-15 prevented apoptosis of activated T cells that effect being associated with the maintenance of Bcl-2, but not of A1 expression. However, restimulation of activated or posteffector T cells with antigenic peptide strongly upregulated A1 mRNA and maintained A1 protein expression. IL-4, IL-7 or IL-15 also prevented cell death of naive T cells. In those cells, cytokines upregulated Bcl-2, but not A1 expression. Therefore, in naive, activated and posteffector T cells, expression of A1 is dependent on TCR but not on cytokine receptor engagement, indicating that A1 is differently regulated from Bcl-xl and Bcl-2.
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Abbreviations
- Ag:
-
antigen
- MAb:
-
monoclonal antibody
- h:
-
hour
- TCR:
-
T-cell receptor
- NP:
-
nucleoprotein
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Acknowledgements
We thank Dr. S Fournel for her help in the preparation of anti-A1/Bfl-1 antiserum. We are very grateful to A Marçais for providing us some mRNA samples as well as to Drs. B Santner-Nanan and E Feoktistova for experiments done with DO11.10 and IL-2-/- DO11.10 mice, and to A Schimpl for helpful discussions. This work is supported by institutional grants from INSERM and additional support from the Association pour la Recherche sur le Cancer (JM and NBB). C Verschelde is supported by a fellowship from the Ministère de l'Éducation et de la Recherche, T Walzer a fellowship from the Association pour la Recherche sur le Cancer and L Quemeneur a fellowship from the Ligue Nationale contre le Cancer.
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Verschelde, C., Walzer, T., Galia, P. et al. A1/Bfl-1 expression is restricted to TCR engagement in T lymphocytes. Cell Death Differ 10, 1059–1067 (2003). https://doi.org/10.1038/sj.cdd.4401265
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DOI: https://doi.org/10.1038/sj.cdd.4401265
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