THE INTERLEUKIN-2 RECEPTOR-ALPHA CHAIN CD25 PROMOTER IS A TARGET FOR NUCLEAR FACTOR OF ACTIVATED T-CELLS/

The expression of the murine interleukin (IL)-2 receptor or chain/CD25 is strongly induced at the transcriptional level after T cell activat ion. We show here that nuclear factor of activated T cell (NF-AT) fact ors are involved in the control of CD25 promoter induction in T cells. NF-ATp and NF-ATc bind to two sites around positions -585 and -650 lo cated upstream of the proximal CD25 promoter. Immediately 3' from thes e NF-AT motifs, nonconsensus sites are located for the binding of AP-1 -like factors. Mutations of sites that suppress NF-AT binding impair t he induction and strong NF-AT-pmediated transactivation of the CD25 pr omoter in T cells. In T lymphocytes from NF-ATp-deficient mice, the ex pression of CD25 is severely impaired, leading to a delayed IL-2 recep tor expression after T cell receptor (TCR)/CD3 stimulation. Our data i ndicate an important role for NF-AT in the faithful expression of high affinity IL-2 receptors and a close link between the TCR-mediated ind uction of IL-2 and IL-2 receptor alpha chain promoters, both of which are regulated by NF-AT factors.