Inhibition of TCR-induced CD8 T cell death by IL-12: regulation of Fas ligand and cellular FLIP expression and caspase activation by IL-12.
In this study we demonstrate the anti-apoptotic effect of IL-12 and its underlying mechanism in CD8 T cells. The prolonged stimulation of CD8 T cells with anti-CD3 alone caused apoptosis mediated by Fas and the caspase signaling pathway. However, costimulation with IL-12 significantly prevented anti-CD3-induced apoptosis of CD8 T cells. IL-12 decreased the number of Fas ligand-positive CD8 T cells and inhibited the activation of caspase-8 and caspase-3. In addition, IL-12 up-regulated cellular FLIPs but not Bcl-2 family proteins or cellular inhibitor of apoptosis proteins. These data suggest that IL-12 provides survival signals to CD8 T cells by down-regulating Fas ligand and up-regulating cellular FLIPs, followed by inhibiting caspase activation, which implies a role for IL-12 in peripheral responses of CD8 T cells in vivo.
Lee
Seung Woo
SW
National Laboratory of DNA Medicine, Division of Molecular and Life Sciences, Pohang University of Science and Technology, Pohang, Korea.
Park
Yunji
Y
Yoo
Jae Kwang
JK
Choi
So Young
SY
Sung
Young Chul
YC
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D017252:CD3 Complex / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D002352:Carrier Proteins / Q000096:biosynthesis*; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D015536:Down-Regulation / Q000276:immunology*; D004789:Enzyme Activation / Q000276:immunology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D053222:Fas Ligand Protein; D005260:Female; D007106:Immune Sera / Q000494:pharmacology; D018664:Interleukin-12 / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D011948:Receptors, Antigen, T-Cell / Q000037:antagonists & inhibitors* / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology; D019014:fas Receptor / Q000378:metabolism
D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D017252:CD3 Complex; D002352:Carrier Proteins; D061945:Caspase Inhibitors; C506387:Cflar protein, mouse; D004791:Enzyme Inhibitors; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D007106:Immune Sera; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008562:Membrane Glycoproteins; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins; D019014:fas Receptor; D018664:Interleukin-12; C505409:Casp3 protein, mouse; C505526:Casp8 protein, mouse; C506434:Casp9 protein, mouse; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases