Abstract
Activation-induced cell death of T cells typically occurs late in the primary response after a prior proliferative response. Here, we describe a novel form of cell death in which purified naive murine CD4+ cells undergo apoptosis within 18 h in vitro after strong TCR ligation. Such rapid-onset TCR-mediated death of T cells does not involve cell division and is Fas-dependent, inhibited by CD28 (and IL-6) costimulation and enhanced by IL-4 and IL-7; by contrast, spontaneous death of CD4+ cells cultured alone is Fas-independent and inhibited by IL-4 and IL-7. TCR-mediated Fas-dependent death of CD4+ cells is prevented by combined TCR/Fas ligation and by drugs that inhibit calcineurin-dependent signaling and mitogen-activated protein kinase MEK1 activation.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antibodies, Monoclonal / metabolism
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Apoptosis / immunology*
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CD4-Positive T-Lymphocytes / cytology*
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism*
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Cell Cycle / immunology
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Cell Differentiation / immunology
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Cells, Cultured
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Cytokines / pharmacology
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Fas Ligand Protein
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Immunologic Memory
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Immunophenotyping
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Intracellular Fluid / immunology
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Ligands
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Lymphocyte Activation*
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Membrane Glycoproteins / biosynthesis
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C3H
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Mice, Inbred C57BL
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Mice, Knockout
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Receptors, Antigen, T-Cell / antagonists & inhibitors
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Receptors, Antigen, T-Cell / immunology
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Receptors, Antigen, T-Cell / metabolism*
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Signal Transduction / immunology
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Species Specificity
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T-Lymphocyte Subsets / cytology
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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / metabolism
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Time Factors
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fas Receptor / immunology
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fas Receptor / metabolism
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fas Receptor / physiology*
Substances
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Antibodies, Monoclonal
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Cytokines
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Fas Ligand Protein
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Fasl protein, mouse
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Ligands
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Membrane Glycoproteins
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Receptors, Antigen, T-Cell
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fas Receptor