Abstract
IL-2 is an important growth and survival factor for T lymphocytes but also sensitizes these cells to Fas-mediated activation-induced cell death (AICD). The molecular basis of these different effects of IL-2 was studied by introducing wild-type and mutant forms of the IL-2 receptor beta (IL-2Rbeta) chain that lacked specific signaling capacities into receptor-deficient T cells by retroviral gene transfer. Activation of Stat5 by IL-2 was found to be involved in T cell proliferation and promoted Fas ligand (FasL) expression and AICD. T cell survival was dependent on a receptor region that activated Akt and the expression of Bcl-2. Thus, distinct IL-2Rbeta chain signaling modules regulate T cell fate by stimulating growth and survival or by promoting apoptosis.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
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Retracted Publication
MeSH terms
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Animals
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Apoptosis / immunology*
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Cell Division
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Cell Survival
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Cells, Cultured
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Fas Ligand Protein
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Gene Transfer Techniques
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Genetic Vectors
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Humans
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Interleukin-2 / immunology*
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Interleukin-2 / pharmacology
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Lymphocyte Activation
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Membrane Glycoproteins / biosynthesis
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mutagenesis
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Receptors, Interleukin-2 / genetics
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Retroviridae
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Signal Transduction / immunology*
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T-Lymphocytes / cytology
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T-Lymphocytes / drug effects
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T-Lymphocytes / immunology*
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fas Receptor / immunology*
Substances
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FASLG protein, human
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Fas Ligand Protein
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Fasl protein, mouse
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Interleukin-2
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Membrane Glycoproteins
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Receptors, Interleukin-2
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fas Receptor