DIFFERENTIAL INTERACTION OF NUCLEAR FACTORS WITH THE PRE-I ENHANCER ELEMENT OF THE HUMAN IL-4 PROMOTER IN DIFFERENT T-CELL SUBSETS

The immunomodulatory cytokine IL-4 affects cells of most hemopoietic l ineages. IL-4 is secreted by activated Th2 but not Th1 cells and plays a major role in the immune response by modulating the differentiation of naive Th cells toward the Th2 phenotype. We have previously identi fied an enhancer element, PRE-I, that is essential for the function of the human IL-4 promoter. To investigate the mechanisms responsible fo r tissue-specific expression of the IL-4 gene, we analyzed nuclear fac tors binding to the PRE-I site and compared the binding activities of these factors to the IL-4 promoter of Th1 and Th2 cells. We show that PRE-I interacts with PMA- and PMA/ionomycin-inducible, cyclosporin A-s ensitive nuclear factors. Using anti-C/EBPP (NF-IL6), anti-C/EBP delta (NF-IL6 beta), anti-NF-ATc, anti-NF-ATp, anti-fos, and anti-Jun Abs w e demonstrate that the previously identified PRE-I binding factor POS- 1 is composed of different transcription factors in different Th cell subsets. In the IL-4-producing Th0-like human Jurkat and mouse EL-4 ce lls, POS-1 (designated POS-1a) contains NF-IL6 beta and Jun. In the mo use Th2 D10 cells and in the human Th2 clones, POS-1. (designated POS- 1b) contains NF-IL6 beta, Jun, and NF-ATc/p. In contrast, POS-1 was no t found in nuclear extracts of human Th1 clones. These findings sugges t that PRE-I may play a role in the differential regulation of IL-4 ge ne expression levels.