Activation of a human T cell line: a two-stimulus requirement in the pretranslational events involved in the coordinate expression of interleukin 2 and gamma-interferon genes.
In the resting state, the T3-positive, human T cell line Jurkat does not synthesize detectable amounts of either interleukin 2 (IL 2) or gamma-interferon (IFN-gamma). Activation of Jurkat as measured by the secretion of substantial amounts of both lymphokines requires two distinct signals. One signal is produced by the phorbol ester, phorbol myristate acetate, and the other by either phytohemagglutinin or antibodies to T3. To elucidate the molecular events by which these activation signals lead to the synthesis of IL 2 and IFN-gamma activity we used cDNA probes to follow the appearance of IL 2 and IFN-gamma-specific transcripts after activation of Jurkat. These studies demonstrate that both signals are required for the appearance of IL 2 or IFN-gamma-specific transcripts and that the appearance of IL 2 and IFN-gamma RNA is coordinate with regard to a) the signals required for their production, b) the kinetics of their appearance, and c) the inhibition of their appearance by cyclosporin A. These studies suggest that distinct T cell-activation signals may operate through a common regulatory pathway involved in the expression of both IL 2 and IFN-gamma genes.
D000911:Antibodies, Monoclonal / Q000502:physiology; D001666:Binding Sites, Antibody / Q000187:drug effects; D002460:Cell Line; D003524:Cyclosporins / Q000494:pharmacology; D005786:Gene Expression Regulation; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics*; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics*; D008213:Lymphocyte Activation; D010835:Phytohemagglutinins / Q000494:pharmacology; D014176:Protein Biosynthesis; D012335:RNA, Ribosomal / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D003524:Cyclosporins; D007376:Interleukin-2; D010835:Phytohemagglutinins; D012335:RNA, Ribosomal; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate