The selective increase in caspase-3 expression in effector but not memory T cells allows susceptibility to apoptosis.
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.
Sabbagh
Laurent
L
Laboratory of Immunology, Université de Montréal, Montreal, Canada.
Kaech
Susan M
SM
Bourbonnière
Martin
M
Woo
Minna
M
Cohen
Luchino Y
LY
Haddad
Elias K
EK
Labrecque
Nathalie
N
Ahmed
Rafi
R
Sékaly
Rafick-Pierre
RP
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology*; D053148:Caspase 3; D020169:Caspases / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D016193:G1 Phase / Q000276:immunology; D007113:Immunity, Innate / Q000235:genetics; D007156:Immunologic Memory / Q000235:genetics; D007376:Interleukin-2 / Q000502:physiology; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000096:biosynthesis; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D016192:Resting Phase, Cell Cycle / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000201:enzymology* / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000201:enzymology* / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D007376:Interleukin-2; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases