Abstract
T cells activated by antigen receptor stimulation in the absence of accessory cell-derived costimulatory signals lose the capacity to synthesize the growth factor interleukin-2 (IL-2), a state called clonal anergy. An analysis of CD3- and CD28-induced signal transduction revealed reduced ERK and JNK enzyme activities in murine anergic T cells. The amounts of ERK and JNK proteins were unchanged, and the kinases could be fully activated in the presence of phorbol 12-myristate 13-acetate. Dephosphorylation of the calcineurin substrate NFATp (preexisting nuclear factor of activated T cells) also remained inducible. These results suggest that a specific block in the activation of ERK and JNK contributes to defective IL-2 production in clonal anergy.
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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CD28 Antigens / immunology
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CD3 Complex / immunology
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
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Clonal Anergy*
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Clone Cells
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Cyclosporine / pharmacology
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DNA-Binding Proteins / metabolism
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Enhancer Elements, Genetic
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Enzyme Activation
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Interleukin-2 / biosynthesis
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Ionomycin / pharmacology
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JNK Mitogen-Activated Protein Kinases
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Lymphocyte Activation
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Mice
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases*
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NFATC Transcription Factors
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Nuclear Proteins*
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Protein-Tyrosine Kinases / metabolism
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Signal Transduction*
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T-Lymphocytes, Helper-Inducer / enzymology
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T-Lymphocytes, Helper-Inducer / immunology*
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Tetradecanoylphorbol Acetate / pharmacology
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Transcription Factor AP-1 / metabolism
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Transcription Factors / metabolism
Substances
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CD28 Antigens
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CD3 Complex
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DNA-Binding Proteins
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Interleukin-2
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NFATC Transcription Factors
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Nuclear Proteins
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Transcription Factor AP-1
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Transcription Factors
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Ionomycin
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Cyclosporine
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Protein-Tyrosine Kinases
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Calcium-Calmodulin-Dependent Protein Kinases
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases
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Tetradecanoylphorbol Acetate