Down regulation of IL 2 mRNA by antibody to the 50-kd protein associated with E receptors on human T lymphocyte.
Recent studies have shown that antibodies to certain epitopes on the 50-kd molecule associated with sheep erythrocyte receptors on human T cells can suppress T cell proliferation and interleukin 2 (IL 2) elaboration. We used a human IL 2 cDNA clone to investigate the effect of antibody 9.6 and cyclosporin A (CsA) on the regulation of IL 2 mRNA levels in the cloned human leukemic T cell line Jurkat, J32. Maximal levels of IL 2 mRNA were reached 6 hr after induction of Jurkat cells with a combination of mitogen phytohemagglutinin (PHA) and phorbol ester (TPA). Antibody 9.6, added during the first 4 hr after lymphocyte stimulation, markedly inhibited IL 2 mRNA accumulation induced by low but synergistic combination of PHA (5 micrograms/ml) and TPA (1.0 ng/ml). The inhibition by 9.6 was not demonstrable as the concentration of PHA or TPA was increased. In contrast, the ability of CsA to suppress IL 2 mRNA accumulation appeared to be independent of PHA or TPA concentration and was minimal if CsA was added 4 hr after stimulation. IL 2 mRNA could be superinduced several folds by addition of cycloheximide 3 hr after induction of J32 with mitogens. Antibody 9.6 did not prevent IL 2 mRNA superinduction induced by cycloheximide, whereas CsA, as well as transcription inhibitor DRB, completely blocked this phenomenon. These findings indicate that signals induced by antibody 9.6 regulate IL 2 production at a pre-translational level, are operative for an extended period of time overlapping with the early phase of IL 2 mRNA accumulation, suppress IL 2 gene expression induced by PHA as well as TPA, and that antibody 9.6 and CsA exert their inhibitory effect by distinct mechanism(s).
D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology*; D001789:Blood Group Antigens / Q000276:immunology*; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D003524:Cyclosporins / Q000494:pharmacology; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007108:Immune Tolerance; D007376:Interleukin-2 / Q000378:metabolism*; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects; D008970:Molecular Weight; D010835:Phytohemagglutinins / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D012756:Sheep; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D001789:Blood Group Antigens; D003524:Cyclosporins; D007376:Interleukin-2; D010835:Phytohemagglutinins; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D003513:Cycloheximide; D013755:Tetradecanoylphorbol Acetate