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Immunity. 2003 Mar;18(3):415-28.

GATA-3 suppresses Th1 development by downregulation of Stat4 and not through effects on IL-12Rbeta2 chain or T-bet.

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1
Mucosal Immunity Section, Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD 20892, USA. wstrober@niaid.nih.gov

Abstract

To further understand the interaction among GATA-3, Stat4, and T-bet in helper T cell development, we first showed that retroviral expression of GATA-3 in developing Th1 cells suppresses Th1 development through downregulation of Stat4 rather through downregulation of the IL-12Rbeta2 chain. Correspondingly, Stat4 levels are greatly suppressed during physiological Th2 development. Then, using cells doubly infected with GFP- and YFP-expressing retroviruses, we showed that retroviral GATA-3 expression in developing Th1 cells does not block Th1 development in cells coexpressing Stat4 but does so in cells coexpressing T-bet. Finally, we showed that retroviral Stat4 expression could facilitate Th2-->Th1 conversion in cells bearing an IL-12Rbeta2 transgene, even in cells lacking T-bet. These findings reassert that Stat4 signaling is a central element of Th1/Th2 development.

PMID:
12648458
[Indexed for MEDLINE]
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