ROLE OF ETS1 IN IL-2 GENE-EXPRESSION

The ETS1 gene encodes a sequence-specific transcription factor binding to purine-rich DNA sequences (-GGAA-) present in the transcriptional regulatory regions of many cellular and viral promoters/enhancers, inc luding many lymphokine genes. The ETS1 gene is expressed at high level s in resting T cells and at very low levels after T cell activation, s uggesting it may suppress the expression of genes induced during T cel l activation. To find out if ETS1 regulates expression of the IL-2 gen e, we have ectopically expressed antisense (AS) ETS1 in jurkat T cells to block the formation of ETS1 proteins. AS ETS1 transfectants produc e higher levels of IL-2 compared with sense ETS1 transfectants. Expres sion of ETS1 DNA binding domain in Jurkat T cells also decreased the p roduction of IL-2. In AS ETS1 transfectants, IL-2 formation was comple tely inhibited by cyclosporin A and FK590. The IL-2 promoter linked to a chloramphenicol acetyl transferase reporter gene has high activity in AS ETS1 transfectants, indicating that increased IL-2 production se ems to be a result of transcriptional induction. Taken together, these results suggest the possibility that ETS1 may act as a negative regul ator of IL-2 gene transcription and provide a rational approach toward engineering the endogenous expression of IL-2 in T cells.