17-β-ESTRADIOL SUPPRESSES IL-2 AND IL-2 RECEPTOR
Abstract Interleukin-2 (IL-2) plays an important role in adaptive immune responses. These responses differ between females and males and may be due to the sex steroid estrogen. In this investigation we show that estrogen suppresses IL-2 production from activated peripheral blood T cells and CD4+ T cell lines at the transcriptional level. Suppression of IL-2 occurred at short term, high 17-β-estradiol concentrations as well as longer term lower 17-β-estradiol concentrations. In CD4+ Jurkat T cells, suppression of IL-2 was associated with decreased nuclear binding of two important IL-2 promoter transcription factors: NFκB and AP-1. The decreased nuclear binding of NFκB occurred in the setting of estrogen-induced increases in IκBα protein levels, an important inhibitor of NFκB nuclear translocation. 17-β-Estradiol was also shown to inhibit IL-2 receptor (IL-2R) expression in activated peripheral blood T cells. Estrogen-induced suppression of IL-2 and its receptor may have many ramifications for our understanding of immune and autoimmune sexual dichotomies, immune responses during pregnancy, and potential therapeutic intervention with hormone agonists and antagonists.