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

J Immunol. 2004 Nov 1;173(9):5425-33. doi: 10.4049/jimmunol.173.9.5425.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • RNA, Messenger / biosynthesis
  • Receptors, Antigen, T-Cell / immunology
  • Resting Phase, Cell Cycle / immunology
  • 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*


  • Epitopes, T-Lymphocyte
  • Interleukin-2
  • RNA, Messenger
  • Receptors, Antigen, T-Cell
  • Casp3 protein, mouse
  • Caspase 3
  • Caspases