Identification of multiple cis-elements and trans-acting factors involved in the induced expression of human IL-2 gene.

Regulated expression of interleukin-2 (IL-2) gene constitutes an essential part in the clonal proliferation of activated T lymphocytes (T-cells). In order to gain insight on the mechanism(s) of the IL-2 gene induction, deletions were introduced in the human IL-2 gene 5'-flanking region and the mitogen inducibility of each deletion mutant was examined in cultured T cell lines. At least four functional regions were identified, they contain potential binding sites for several transcription factors including one NF-kappa B and two octamer binding factor sites. Whereas each of the functional regions (or elements) is required for the maximal induction of the IL-2 gene by mitogen, one such region was found to be dispensable for activation by the HTLV-1-encoded trans-activator, tax-1. Furthermore, the potent immunosuppressive agent, cyclosporin A was found to inhibit the gene induction by mitogen, but not by tax-1.