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A Transcriptional Block in the IL-2 Promoter at the -150 AP-1 Site in Effector CD8⁺ T Cells¹

Rosalynde J. Finch^*, Patrick E. Fields^2, and Philip D. Greenberg^3,*,,

Department of ^* Immunology and Medicine, University of Washington, Seattle, WA 98195; Fred Hutchinson Cancer Research Center, Seattle, WA 98109; and Committee on Immunology, University of Chicago, Chicago, IL 60637

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.

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