Molecular regulation of human interleukin 2 and T-cell function by interleukin 4.
Distinct functional T-cell subsets, differing in the patterns of lymphokines produced, regulate cell-mediated and humoral immune responses. The two major types and their principal products, interleukin 4 and interferon gamma (IL-4 and IFN-gamma), are reciprocally negatively interactive. To analyze the molecular mechanism of IL-4-mediated suppression of cell-mediated immunity we studied its effects on expression of interleukin 2 (IL-2) and IFN-gamma. IL-4 pretreatment of Jurkat cells prior to stimulation resulted in a decrease in transcription of the IL2 gene. IL-4 suppressed IL-2 and IFN-gamma mRNA levels in primary human T cells, and addition of anti-CD28 antibodies relieved this suppression. Using enhancer-reporter constructs, IL-4 specifically down-regulated the NFIL-2B element. Electrophoretic mobility shift assays using a DNA oligomer containing the NFIL-2B binding site indicated that IL-4 inhibited the NFIL-2B complex and that the NFIL-2B DNA binding factor is distinct from AP-1. These results suggest that IL-4 may regulate development and function of T-cell subsets involved in cell-mediated immunity in part by inhibiting factors required for transcription of the IL2 gene.
Schwarz
E M
EM
Howard Hughes Medical Institute, Albert Einstein College of Medicine, Bronx, NY 10461.
Salgame
P
P
Bloom
B R
BR
D000199:Actins / Q000096:biosynthesis; D001483:Base Sequence; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004742:Enhancer Elements, Genetic / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000235:genetics; D015847:Interleukin-4 / Q000494:pharmacology*; D007700:Kinetics; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D010957:Plasmids; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D000199:Actins; D007376:Interleukin-2; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014157:Transcription Factors; D015847:Interleukin-4; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate