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The Journal of Immunology, Vol 154, Issue 12 6397-6405, Copyright © 1995 by American Association of Immunologists
ARTICLES |
MR Hodge, JW Rooney and LH Glimcher
Department of Cancer Biology, Harvard School of Public Health, Boston, MA 02115, USA.
Immune responses to pathogens often lead to the generation of polarized T helper subsets designated Th1 and Th2. Th1 cells, characterized by the production of IL-2 and IFN-gamma, stimulate cellular immune responses important for protection against intracellular pathogens. In contrast, Th2 cells, which produce IL-4, are potent stimulators of B cells and stimulate protection against extracellular pathogens. IL-4 has also emerged as a key cytokine in T cell differentiation since it has been shown to direct the development of naive T cells toward a Th2 phenotype. Recent studies have provided insights into the transcriptional regulation of IL-4, including the identification of multiple binding sites for a subunit of the IL-2 transcription factor NF-AT. In this study we describe the characterization of an essential region of the IL-4 promoter located immediately upstream of the TATA element. High-resolution mutagenesis of this 33-bp region revealed multiple sites indispensable for inducible IL-4 transcription. Included in this region are overlapping binding sites for the cyclosporin A- sensitive factor NF-ATp and a novel constitutively expressed factor designated PCC. An additional sequence adjacent to the TATA element is also shown to be critical for IL-4 transcription in Th2 cells.
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