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 recognit ion have been isolated. However, most effector CD8+ T cells recovered after exposure to Ag do not produce sufficient IL-2 to sustain growth, and depen d 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, b ut mechanisms restricting IL-2 production in CD8(+) T cells have not been e lucidated. To evaluate transcriptional regulation of the IL-2 gene in CD8() T cells, we stably transfected reporter genes into Ag-specific CD8(+) T c ell clones. CD28(+) CD8(+) T cells unable to transcribe the IL-2 gene in re sponse 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 tra nsactivate 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 sit e, or insertion of a CD28RE/AP-1 consensus site upstream of the native - 15 0 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 promote r.