Abstract
IL-2 gene transcription in T cells requires both TCR and costimulatory signals. IL-2 promoter activation in Jurkat T cells stimulated with superantigen presented by Raji B cells requires CD28 activation. The addition of rCTLA4Ig, which blocks CD28 binding to its ligand, to the cultures decreased IL-2 promoter activation by >80%. Interestingly, CTLA4Ig did not significantly inhibit the activation of either NF of activated T cells (NFAT) or AP-1 reporters. Therefore, activation of NFAT and AP-1 is insufficient for IL-2 promoter activation. In contrast, an RE/AP reporter was blocked by CTLA4Ig by >90%. Thus, the requirement for CD28 in IL-2 promoter activation appears to be due to RE/AP and not the NFAT or AP-1 sites. In addition, these data suggest that transcriptional activation of RE/AP is not mediated by NFAT, because activation of a NFAT reporter is not affected by the addition of CTLA4Ig.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Abatacept
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Antigens, Bacterial / immunology
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Antigens, CD
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Antigens, Differentiation / pharmacology
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B-Lymphocytes / drug effects
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B-Lymphocytes / metabolism
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Burkitt Lymphoma / pathology
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CD28 Antigens / physiology*
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CTLA-4 Antigen
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Cells, Cultured
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DNA-Binding Proteins / physiology*
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Enterotoxins / immunology
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Gene Expression Regulation*
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Genes, Reporter
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Humans
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Immunoconjugates*
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Interleukin-2 / biosynthesis*
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Interleukin-2 / genetics
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Jurkat Cells
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Luciferases / biosynthesis
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Luciferases / genetics
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Lymphocyte Activation*
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Lymphocyte Cooperation*
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Lymphocytes
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NFATC Transcription Factors
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Nuclear Proteins*
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Promoter Regions, Genetic*
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Recombinant Fusion Proteins / biosynthesis
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Recombinant Fusion Proteins / genetics
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Regulatory Sequences, Nucleic Acid*
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Superantigens / immunology
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T-Lymphocytes / drug effects
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T-Lymphocytes / metabolism
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Tacrolimus / pharmacology
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Transcription Factor AP-1 / physiology*
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Transcription Factors / physiology*
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Transcription, Genetic* / drug effects
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Tumor Cells, Cultured
Substances
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Antigens, Bacterial
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Antigens, CD
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Antigens, Differentiation
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CD28 Antigens
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CTLA-4 Antigen
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CTLA4 protein, human
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DNA-Binding Proteins
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Enterotoxins
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Immunoconjugates
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Interleukin-2
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NFATC Transcription Factors
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Nuclear Proteins
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Recombinant Fusion Proteins
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Superantigens
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Transcription Factor AP-1
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Transcription Factors
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enterotoxin E, Staphylococcal
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Abatacept
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Luciferases
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Tacrolimus