title: Differential regulation of interleukin 4 and interleukin 5 gene expression: a comparison of T-cell gene induction by anti-CD3 antibody or by exogenous lymphokines.
abstract: Murine T helper type 2 clones were stimulated with immobilized anti-CD3 antibody or with recombinant lymphokines to compare the expression of T-cell activation genes induced by these stimuli. Immobilized anti-CD3 antibody, recombinant interleukin 2 (IL-2), and recombinant interleukin 4 (IL-4) all induced proliferation of the T helper type 2 clones 10-5-17 and D10. Proliferation of these clones induced by anti-CD3 antibody was completely inhibited by cyclosporine A, whereas cyclosporine A had little effect on proliferation induced by recombinant IL-2 or recombinant IL-4. Both immobilized anti-CD3 antibody, and recombinant IL-2 induced the expression of the protooncogenes c-myc and c-myb. Immobilized anti-CD3 antibody also induced expression of the lymphokine genes IL-4, interleukin 5 (IL-5), and granulocyte-macrophage colony-stimulating factor. In contrast, recombinant IL-2 induced IL-5 mRNA expression but did not induce detectable expression of IL-4 or granulocyte-macrophage colony-stimulating factor mRNA. Likewise, recombinant IL-4 induced expression of IL-5 but not IL-4 mRNA. Thus, the IL-4 and IL-5 genes appear to be differentially regulated after stimulation with recombinant lymphokines. Effects of cyclosporine A and the protein synthesis inhibitors cycloheximide and anisomycin on IL-4 and IL-5 gene expression suggest that these genes are activated by different pathways after anti-CD3 stimulation. Cyclosporine A completely inhibited anti-CD3-induced expression of IL-4 mRNA but not of IL-5 mRNA, and protein-synthesis inhibitors completely inhibited induction of IL-5 mRNA but not of IL-4 mRNA. Together, our data show that T-cell receptor-mediated and lymphokine receptor-mediated signals induce different patterns of lymphokine gene expression and provide strong evidence that the IL-4 and IL-5 genes are differently regulated.
authors: Howard Hughes Medical Institute, Bethesda, MD 20814.
authors: P R
authors: PR
authors: Bohjanen
authors: M
authors: M
authors: Okajima
authors: R J
authors: RJ
authors: Hodes
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D015152:Blotting, Northern; D017252:CD3 Complex; D002460:Cell Line; D002999:Clone Cells; D003513:Cycloheximide / Q000494:pharmacology; D003524:Cyclosporins / Q000494:pharmacology; D015342:DNA Probes; D005786:Gene Expression Regulation / Q000187:drug effects; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000235:genetics* / Q000494:pharmacology; D015848:Interleukin-5 / Q000235:genetics*; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D011994:Recombinant Proteins / Q000494:pharmacology; D015183:Restriction Mapping; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D015533:Transcriptional Activation
chemical_list: D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D003524:Cyclosporins; D015342:DNA Probes; D007376:Interleukin-2; D015848:Interleukin-5; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins; D015847:Interleukin-4; D003513:Cycloheximide