Fas costimulation of naïve CD4 T cells is controlled by NF-κB signaling and caspase activity

Journal of Leukocyte Biology

Thomas S. Söderström⁴  Arno Hänninen²  John E. Eriksson³  Sirpa Jalkanen²  Mikael Maksimow¹ 

[1] MediCity Research Laboratory and Department of Medical Microbiology, University of Turku, and National Public Health Institute, Turku, Finland; Turku Graduate School of Biomedical Sciences, Finland MediCity Research Laboratory and Department of Medical Microbiology, University of Turku, and National Public Health Institute, Turku, Finland; MediCity Research Laboratory and Department of Medical Microbiology, University of Turku, and National Public Health Institute, Turku, Finland; Turku Graduate School of Biomedical Sciences, Finland Turku Graduate School of Biomedical Sciences, Finland MediCity Research Laboratory and Department of Medical Microbiology, University of Turku, and National Public Health Institute, Turku, Finland; Turku Graduate School of Biomedical Sciences, FinlandMediCity Research Laboratory and Department of Medical Microbiology, University of Turku, and National Public Health Institute, Turku, Finland; MediCity Research Laboratory and Department of Medical Microbiology, University of Turku, and National Public Health Institute, Turku, Finland; MediCity Research Laboratory and Department of Medical Microbiology, University of Turku, and National Public Health Institute, Turku, Finland;;Turku Centre for Biotechnology, University of Turku, and Ã…bo Akademi University, Finland; Department of Biology, Laboratory of Animal Physiology, University of Turku, Finland; and Turku Centre for Biotechnology, University of Turku, and Ã…bo Akademi University, Finland; Turku Centre for Biotechnology, University of Turku, and Ã…bo Akademi University, Finland; Department of Biology, Laboratory of Animal Physiology, University of Turku, Finland; and Department of Biology, Laboratory of Animal Physiology, University of Turku, Finland; and Turku Centre for Biotechnology, University of Turku, and Ã…bo Akademi University, Finland; Department of Biology, Laboratory of Animal Physiology, University of Turku, Finland; and;Turku Centre for Biotechnology, University of Turku, and Ã…bo Akademi University, Finland; Department of Biology, Ã…bo Akademi University, Turku, Finland; Turku Graduate School of Biomedical Sciences, Finland Turku Centre for Biotechnology, University of Turku, and Ã…bo Akademi University, Finland; Turku Centre for Biotechnology, University of Turku, and Ã…bo Akademi University, Finland; Department of Biology, Ã…bo Akademi University, Turku, Finland; Turku Graduate School of Biomedical Sciences, Finland Department of Biology, Ã…bo Akademi University, Turku, Finland; Turku Centre for Biotechnology, University of Turku, and Ã…bo Akademi University, Finland; Department of Biology, Ã…bo Akademi University, Turku, Finland; Turku Graduate School of Biomedical Sciences, Finland Turku Graduate School of Biomedical Sciences, Finland Turku Centre for Biotechnology, University of Turku, and Ã…bo Akademi University, Finland; Department of Biology, Ã…bo Akademi University, Turku, Finland; Turku Graduate School of Biomedical Sciences, Finland

关键词: T cell activation;    lymphocyte;    apoptosis;    dendritic cell;    cell proliferation;   

DOI  :  10.1189/jlb.0505238

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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-γ (IFN-γ) production. To understand this costimulation, we investigated the roles of caspases and nuclear factor (NF)-κB 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-κB simultaneously with Fas ligation inhibited the increased IFN-γ 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-κB acts as a dominant survival-supporting factor of Fas-costimulated cells containing high levels of activated caspase-8 and -3.

【 授权许可】

Unknown