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, IFNgamma. T-bet expression correlates with IFNgamma expression in Th1 and NK cells. Ectopic expression of T-bet both transactivates the IFNgamma gene and induces endogenous IFNgamma 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 IFNgamma 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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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B-Lymphocytes / physiology
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Base Sequence
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Cell Differentiation / immunology
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Cell Lineage / physiology
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Cell Polarity / immunology
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Cloning, Molecular
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Flow Cytometry
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Gene Expression / immunology
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Genes, Reporter
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Green Fluorescent Proteins
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Indicators and Reagents / metabolism
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Interferon-gamma / genetics
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Interleukin-4 / genetics
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Interleukin-5 / genetics
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Killer Cells, Natural / physiology
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Luminescent Proteins / genetics
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Mice
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Mice, Inbred BALB C
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Mice, Transgenic
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Molecular Sequence Data
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Signal Transduction / immunology
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T-Box Domain Proteins
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T-bet Transcription Factor
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Th1 Cells / chemistry
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Th1 Cells / cytology*
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Th1 Cells / immunology
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Th2 Cells / cytology
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Th2 Cells / immunology
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Transcription Factors / genetics*
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Transcription Factors / metabolism
Substances
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Indicators and Reagents
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Interleukin-5
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Luminescent Proteins
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T-Box Domain Proteins
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T-bet Transcription Factor
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Transcription Factors
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Green Fluorescent Proteins
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Interleukin-4
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Interferon-gamma
Associated data
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GENBANK/AF241242
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GENBANK/AF241243