Effect of CD28 signal transduction on c-Rel in human peripheral blood T cells.
Optimal T-cell activation requires both an antigen-specific signal delivered through the T-cell receptor and a costimulatory signal which can be delivered through the CD28 molecule. CD28 costimulation induces the expression of multiple lymphokines, including interleukin 2 (IL-2). Because the c-Rel transcription factor bound to and activated the CD28 response element within the IL-2 promoter, we focused our study on the mechanism of CD28-mediated regulation of c-Rel in human peripheral blood T cells. We showed that CD28 costimulation accelerated the kinetics of nuclear translocation of c-Rel (and its phosphorylated form), p50 (NFKB1), and p65 (RelA). The enhanced nuclear translocation of c-Rel correlated with the stimulation of Il-2 production and T-cell proliferation by several distinct anti-CD28 monoclonal antibodies. This is explained at least in part by the long-term downregulation of I kappa B alpha following CD28 signalling as opposed to phorbol myristate acetate alone. Furthermore, we showed that the c-Rel-containing CD28-responsive complex is enhanced by, but not specific to, CD28 costimulation. Our results indicate that c-Rel is one of the transcription factors targeted by CD28 signalling.
Department of Microbiology and Immunology, Baylor College of Medicine, Houston, Texas 77030.
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Bryan
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Li
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Lai
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Van
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Rice
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Rich
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Tan
D001483:Base Sequence; D018106:CD28 Antigens / Q000502:physiology*; D002451:Cell Compartmentation; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D020672:I-kappa B Proteins; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D000072000:NF-KappaB Inhibitor alpha; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D020569:Proto-Oncogene Proteins c-rel; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism
D018106:CD28 Antigens; D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D007376:Interleukin-2; C000606204:NFKBIA protein, human; D009838:Oligodeoxyribonucleotides; D011518:Proto-Oncogene Proteins; D020569:Proto-Oncogene Proteins c-rel; D014157:Transcription Factors; D000072000:NF-KappaB Inhibitor alpha; D013755:Tetradecanoylphorbol Acetate