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The Journal of Immunology, 2004, 173: 5425-5433.
Copyright © 2004 by The American Association of Immunologists

The Selective Increase in Caspase-3 Expression in Effector but Not Memory T Cells Allows Susceptibility to Apoptosis1

Laurent Sabbagh2,*, Susan M. Kaech3,**, Martin Bourbonnière3,*,{dagger}, Minna Woo{dagger}{dagger}, Luchino Y. Cohen*,{dagger},§, Elias K. Haddad*,{ddagger}, Nathalie Labrecque§,#, Rafi Ahmed** and Rafick-Pierre Sékaly4,*,{dagger},{ddagger},||

* Laboratory of Immunology, {dagger} Département de Microbiologie et d’Immunologie and {ddagger} Centre de Recherche du Centre Hospitalier de l’Université de Montréal, and § Département de Médecine, Université de Montréal, Montreal, Canada; Department of Microbiology and Immunology and || Faculty of Medicine, Division of Experimental Medicine, McGill University, Montreal, Canada; # Guy-Bernier Research Center, Maisonneuve-Rosemont Hospital, Montreal, Canada; ** Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322; and {dagger}{dagger} Ontario Cancer Institute, Department of Medicine, University of Toronto, Toronto, Canada

Caspases play a central role in T lymphocyte activation and death. We have demonstrated previously that caspase-3, an effector molecule for activation-induced cell death (AICD), is processed following T cell activation in the absence of apoptosis. We report in this study that caspase-3 mRNA levels were selectively increased in peripheral T cells, following Ag receptor-mediated activation. The up-regulation of caspase-3 mRNA was confined to cells in the early phases of the cell cycle (G0/G1) and was independent of IL-2 signaling. This increase led to the renewal of procaspase-3 as evidenced by a 6-fold up-regulation of the zymogen in nonapoptotic stimulated T cells. The increase of mRNA levels and of both the zymogen and the cleaved forms of caspase-3 was observed in in vivo stimulated Ag-specific effector, but not memory T cells, correlating with the enhanced susceptibility of effector T cells to AICD. Furthermore, we confirm that caspase-3 levels directly influence the sensitivity of activated T cells to apoptosis, as shown using T lymphocytes isolated from caspase-3 heterozygous and knockout mice. These findings indicate that the selective up-regulation of caspase-3 transcription is required to maintain the cytoplasmic levels of this protease, which control AICD and T cell homeostasis.




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