Effector CD4+ T cells generate intermediate caspase activity and cleavage of caspase-8 substrates.
Caspase-8 activation promotes cell apoptosis but is also essential for T cell activation. The extent of caspase activation and substrate cleavage in these divergent processes remains unclear. We show that murine effector CD4(+) T cells generated levels of caspase activity intermediate between unstimulated T cells and apoptotic populations. Both caspase-8 and caspase-3 were partially activated in effector T cells, which was reflected in cleavage of the caspase-8 substrates, c-FLIP(L), receptor interacting protein 1, and to a lesser extent Bid, but not the caspase-3 substrate inhibitor of caspase-activated DNase. Th2 effector CD4(+) T cells manifested more caspase activity than did Th1 effectors, and caspase blockade greatly decreased initiation of cell cycling. The current findings define the level of caspase activity and substrates during initiation of T cell cycling.
Misra
Ravi S
RS
University of Vermont, Immunobiology Program, College of Medicine, Burlington, VT 05405, USA.
Jelley-Gibbs
Dawn M
DM
Russell
Jennifer Q
JQ
Huston
Gail
G
Swain
Susan L
SL
Budd
Ralph C
RC
D000818:Animals; D051023:BH3 Interacting Domain Death Agonist Protein; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D002352:Carrier Proteins / Q000378:metabolism; D053148:Caspase 3; D053181:Caspase 8; D020169:Caspases / Q000378:metabolism*; D004789:Enzyme Activation / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011506:Proteins / Q000378:metabolism; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; D013379:Substrate Specificity; D006377:T-Lymphocytes, Helper-Inducer / Q000201:enzymology*
D051023:BH3 Interacting Domain Death Agonist Protein; C494815:Bid protein, mouse; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D002352:Carrier Proteins; C506387:Cflar protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; C506251:Ripk1 protein, mouse; C505409:Casp3 protein, mouse; C505526:Casp8 protein, mouse; D053148:Caspase 3; D053181:Caspase 8; D020169:Caspases