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The selective increase in caspase-3 expression in effector but not memory T cells allows susceptibility to apoptosis
Journal article   Open access   Peer reviewed

The selective increase in caspase-3 expression in effector but not memory T cells allows susceptibility to apoptosis

Laurent Sabbagh, Susan M Kaech, Martin Bourbonnière, Minna Woo, Luchino Y Cohen, Elias K Haddad, Nathalie Labrecque, Rafi Ahmed and Rafick-Pierre Sékaly
The Journal of immunology (1950), v 173(9), pp 5425-5433
01 Nov 2004
DOI: https://doi.org/10.4049/jimmunol.173.9.5425
PMID: 15494489
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
http://www.jimmunol.org/content/173/9/5425.full.pdfView
Published, Version of Record (VoR) Open
url
https://doi.org/10.4049/jimmunol.173.9.5425View
Published, Version of Record (VoR) Open

Abstract

Animals Apoptosis - genetics Apoptosis - immunology Caspase 3 Caspases - biosynthesis Caspases - deficiency Caspases - genetics Caspases - metabolism Enzyme Activation - immunology Epitopes, T-Lymphocyte - immunology G1 Phase - immunology Immunity, Innate - genetics Immunologic Memory - genetics Interleukin-2 - physiology Lymphocyte Activation - genetics Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Receptors, Antigen, T-Cell - immunology Resting Phase, Cell Cycle - immunology RNA, Messenger - biosynthesis T-Lymphocyte Subsets - cytology T-Lymphocyte Subsets - enzymology T-Lymphocyte Subsets - immunology T-Lymphocytes, Regulatory - cytology T-Lymphocytes, Regulatory - enzymology T-Lymphocytes, Regulatory - immunology Up-Regulation - immunology
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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Web of Science research areas
Immunology
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