TRANSCRIPTIONAL REPRESSION OF THE IL-2 GENE IN TH CELLS BY ZEB

Th1- and Th2-type cells mediate distinct effector functions via cytoki ne secretion in response to immunologic challenge. Precursor Th cells transcribe IFN-gamma, IL-2, and IL-4 upon activation. Repeated stimula tion of Th precursor cells in the presence of IL-4 leads to terminally differentiated Th2 cells that have lost the ability to transcribe the IL-2 gene. We provide evidence that repression of IL-2 gene expressio n in Th2 cells and partial repression in Th1 cells are mediated by ZEB , a zinc finger, E box-binding transcription factor. This factor binds to a negative regulatory element, NRE-A, in the IL-2 promoter, thereb y acting as a potent repressor of IL-2 transcription.