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The Journal of Immunology, 1998, 160: 4433-4440.
Copyright © 1998 by The American Association of Immunologists

Transcriptional Repression of the IL-2 Gene in Th Cells by ZEB1

Dag H. Yasui*, Tom Genetta{dagger}, Tom Kadesch{dagger}, Thomas M. Williams{ddagger}, Susan L. Swain§, Lisa V. Tsui§ and Brigitte T. Huber2,*

* Program in Immunology, Department of Pathology, Tufts University School of Medicine, Boston, MA 02111; {dagger} Howard Hughes Medical Institute and Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, PA 19704; {ddagger} Department of Pathology, School of Medicine, University of New Mexico, Albuquerque, NM 87131; and § Trudeau Institute, Saranac Lake, NY 12983

Th1- and Th2-type cells mediate distinct effector functions via cytokine secretion in response to immunologic challenge. Precursor Th cells transcribe IFN-{gamma}, IL-2, and IL-4 upon activation. Repeated stimulation 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 expression 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, thereby acting as a potent repressor of IL-2 transcription.




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