Fas costimulation of naive CD4 T cells is controlled by NF-kappaB signaling and caspase activity.
Fas ligation induces apoptosis of activated T cells via the caspase cascade but can also mediate costimulatory signals to naïve T cells at the time of activation. We have previously shown that Fas ligation of naïve CD4 T cells activated by dendritic cells induces death or accelerates their proliferation and increases interferon-gamma (IFN-gamma) production. To understand this costimulation, we investigated the roles of caspases and nuclear factor (NF)-kappaB in survival and proliferation of responding T cells. Fas ligation increased caspase-3 and -8 activities during T cell activation, irrespective of cell fate. The accelerated proliferation induced by Fas ligation could be reduced by selective inhibition of both caspases. Inhibition of NF-kappaB simultaneously with Fas ligation inhibited the increased IFN-gamma production and caused uniform death of all responding T cells. Thus, Fas-mediated costimulation of naïve CD4 T cells is driven by active caspases, and NF-kappaB acts as a dominant survival-supporting factor of Fas-costimulated cells containing high levels of activated caspase-8 and -3.
Maksimow
Mikael
M
University of Turku, Tykistökatu 6A, 20520 Turku, Finland. arno.hanninen@utu.fi
Söderström
Thomas S
TS
Jalkanen
Sirpa
S
Eriksson
John E
JE
Hänninen
Arno
A
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D053148:Caspase 3; D053181:Caspase 8; D020169:Caspases / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D053222:Fas Ligand Protein; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051379:Mice; D016328:NF-kappa B / Q000494:pharmacology / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D000079424:Tumor Necrosis Factor Inhibitors; D048069:Tumor Necrosis Factors / Q000494:pharmacology*
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D000079424:Tumor Necrosis Factor Inhibitors; D048069:Tumor Necrosis Factors; D007371:Interferon-gamma; C505409:Casp3 protein, mouse; C505526:Casp8 protein, mouse; D053148:Caspase 3; D053181:Caspase 8; D020169:Caspases