Abstract
Activation-induced cell death (AICD) plays an essential role in the contraction of activated T cells after eradication of pathogen. Fas (APO-1/CD95) is one of the key cell surface proteins that mediate AICD in CD4(+) and CD8(+) T cells. Despite its prime importance in cell death, regulation of Fas expression in T cells is poorly understood. Here we show that Cyclon, a newly identified cytokine-inducible protein, is induced in T cells on T-cell receptor ligation and important for immune homeostasis. Transgenic expression of Cyclon ameliorated autoimmune phenotype in mice lacking subunits of IL-2R. Transgenic expression of Cyclon markedly enhanced AICD through increased expression of Fas whose expression is essential for Cyclon action. Finally, we demonstrated that activated but not resting CD4(+) T cells with targeted deletion of a Cyclon allele show reduced AICD and expression of Fas, indicating a critical role of Cyclon in Fas expression in activated T cells. We think that our data provide insight into expression regulation of Fas in T cells.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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CD4-Positive T-Lymphocytes / immunology*
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CD4-Positive T-Lymphocytes / metabolism
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CD8-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / metabolism
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Cell Death / genetics
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Cell Death / immunology
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Gene Expression Regulation / genetics
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Gene Expression Regulation / immunology*
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Gene Knockdown Techniques
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Homeostasis / genetics
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Homeostasis / immunology*
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Lymphocyte Activation / genetics
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Lymphocyte Activation / immunology*
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Mice
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Mice, Knockout
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Nuclear Proteins / genetics
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Nuclear Proteins / immunology*
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Nuclear Proteins / metabolism
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Receptors, Antigen, T-Cell / genetics
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Receptors, Antigen, T-Cell / immunology
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Receptors, Antigen, T-Cell / metabolism
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Receptors, Interleukin-2 / genetics
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Receptors, Interleukin-2 / immunology
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Receptors, Interleukin-2 / metabolism
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fas Receptor / biosynthesis
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fas Receptor / genetics
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fas Receptor / immunology*
Substances
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Fas protein, mouse
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Nuclear Proteins
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Receptors, Antigen, T-Cell
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Receptors, Interleukin-2
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cyclon protein, mouse
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fas Receptor