A transcriptional block in the IL-2 promoter at the -150 AP-1 site in effector CD8+ T cells.
Both CD4+ and CD8+ T cells that produce IL-2 in response to Ag recognition have been isolated. However, most effector CD8+ T cells recovered after exposure to Ag do not produce sufficient IL-2 to sustain growth, and depend on CD4+ T helper cells for this obligate growth factor. IL-2 expression in CD4+ T cells is primarily controlled at the level of transcription, but mechanisms restricting IL-2 production in CD8+ T cells have not been elucidated. To evaluate transcriptional regulation of the IL-2 gene in CD8+ T cells, we stably transfected reporter genes into Ag-specific CD8+ T cell clones. CD28+ CD8(+) T cells unable to transcribe the IL-2 gene in response to antigenic stimulation had a block in transactivation of the -150 CD28 response element (CD28RE)/AP-1 site of the IL-2 promoter, but did transactivate the composite NFAT/AP-1 and OCT/AP-1 sites, and a consensus AP-1 motif. Mutation of the nonconsensus -150 AP-1 site to a consensus AP-1 site, or insertion of a CD28RE/AP-1 consensus site upstream of the native -150 CD28RE/AP-1 site restored transactivation of the altered promoter. These results suggest that the defect at the -150 site may reflect the absence or inactivity of a required factor rather than repression of the IL-2 promoter.
Finch
R J
RJ
Department of Immunology, University of Washington, Seattle, WA 98195, USA.
Fields
P E
PE
Greenberg
P D
PD
D020121:5' Untranslated Regions / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D020816:Amino Acid Motifs / Q000235:genetics; D000818:Animals; D000941:Antigens / Q000276:immunology; D001665:Binding Sites / Q000235:genetics / Q000276:immunology; D018106:CD28 Antigens / Q000096:biosynthesis / Q000235:genetics; D017252:CD3 Complex / Q000096:biosynthesis; D016827:CD8 Antigens / Q000096:biosynthesis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D002999:Clone Cells; D016384:Consensus Sequence / Q000235:genetics; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D016297:Mutagenesis, Site-Directed; D011401:Promoter Regions, Genetic / Q000276:immunology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020218:Response Elements / Q000235:genetics / Q000276:immunology; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D014158:Transcription, Genetic / Q000276:immunology*; D015533:Transcriptional Activation / Q000276:immunology; D014407:Tumor Cells, Cultured
D020121:5' Untranslated Regions; D000941:Antigens; D018106:CD28 Antigens; D017252:CD3 Complex; D016827:CD8 Antigens; D007376:Interleukin-2; D012333:RNA, Messenger; D018808:Transcription Factor AP-1