Transcriptional regulation of the interleukin-2 gene in normal human peripheral blood T cells. Convergence of costimulatory signals and differences from transformed T cells.
To study transcriptional regulation in normal human T cells, we have optimized conditions for transient transfection. Interleukin-2 (IL-2) promoter-reporter gene behavior closely parallels the endogenous gene in response to T cell receptor and costimulatory signals. As assessed with mutagenized promoters, the most important IL-2 cis-regulatory elements in normal T cells are the proximal AP-1 site and the NF- kappaB site. Both primary activation, with phytohemagglutinin or antibodies to CD3, and costimulation, provided by pairs of CD2 antibodies or B7-positive (B cells) or B7-negative (endothelial) accessory cells, are mediated through the same cis-elements. Interestingly, the nuclear factor of activated T cell sites are much less important in normal T cells than in Jurkat T cells. We conclude that IL-2 transcriptional regulation differs in tumor cell lines compared with normal T cells and that different costimulatory signals converge on the same cis-elements in the IL-2 promoter.
Hughes
C C
CC
Molecular Cardiobiology Program, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, Connecticut 06536, USA.
Pober
J S
JS
D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D001665:Binding Sites; D017252:CD3 Complex / Q000276:immunology / Q000502:physiology; D002461:Cell Line, Transformed; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics*; D007700:Kinetics; D008156:Luciferases / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D017252:CD3 Complex; D007376:Interleukin-2; D016328:NF-kappa B; D011994:Recombinant Proteins; D014157:Transcription Factors; D008156:Luciferases