Inhibition of activation of transcription factor AP-1 by CD28 signalling in human T-cells.
Co-stimulation of T-lymphocytes by T-cell receptor (TcR) occupancy and activation of the CD28 surface molecule results in enhanced proliferation and interleukin 2 (IL-2) production. The increase in IL-2 gene expression triggered by CD28 involves a kappa B-like sequence in the 5'-regulatory region of the IL-2 promoter, called CD28-responsive element. Stimulation of T-cells by agonistic anti-CD28 antibodies in conjunction with phorbol 12-myristate 13-acetate (PMA)- or TcR-derived signals induces the enhanced activation of the transcription factor NF-kappa B. Here we report that CD28 engagement, however, exerts opposite effects on the transcription factor AP-1. Whereas anti-CD28 together with PMA increased the DNA binding and trans-activation activity of NF-kappa B, PMA-induced activation of AP-1 was significantly suppressed. The inhibitory effect exerted by anti-CD28 was observed at the level of DNA binding as well as in functional reporter-gene assays. These results suggest that the two transcription factors are independently regulated and may perform different functions during T-cell activation.
Los
M
M
Division of Immunochemistry, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
Dröge
W
W
Schulze-Osthoff
K
K
D001483:Base Sequence; D018106:CD28 Antigens / Q000378:metabolism*; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D009838:Oligodeoxyribonucleotides; D016755:Proto-Oncogene Proteins c-jun / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D018106:CD28 Antigens; D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; D016755:Proto-Oncogene Proteins c-jun; D004247:DNA; D013755:Tetradecanoylphorbol Acetate