[HTML][HTML] A novel transcription factor, T-bet, directs Th1 lineage commitment

SJ Szabo, ST Kim, GL Costa, X Zhang, CG Fathman… - Cell, 2000 - cell.com
SJ Szabo, ST Kim, GL Costa, X Zhang, CG Fathman, LH Glimcher
Cell, 2000cell.com
Naive T helper cells differentiate into two subsets, Th1 and Th2, each with distinct functions
and cytokine profiles. Here, we report the isolation of T-bet, a Th1-specific T box transcription
factor that controls the expression of the hallmark Th1 cytokine, IFNγ. T-bet expression
correlates with IFNγ expression in Th1 and NK cells. Ectopic expression of T-bet both
transactivates the IFNγ gene and induces endogenous IFNγ production. Remarkably,
retroviral gene transduction of T-bet into polarized Th2 and Tc2 primary T cells redirects …
Abstract
Naive T helper cells differentiate into two subsets, Th1 and Th2, each with distinct functions and cytokine profiles. Here, we report the isolation of T-bet, a Th1-specific T box transcription factor that controls the expression of the hallmark Th1 cytokine, IFNγ. T-bet expression correlates with IFNγ expression in Th1 and NK cells. Ectopic expression of T-bet both transactivates the IFNγ gene and induces endogenous IFNγ production. Remarkably, retroviral gene transduction of T-bet into polarized Th2 and Tc2 primary T cells redirects them into Th1 and Tc1 cells, respectively, as evidenced by the simultaneous induction of IFNγ and repression of IL-4 and IL-5. Thus, T-bet initiates Th1 lineage development from naive Thp cells both by activating Th1 genetic programs and by repressing the opposing Th2 programs.
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