A Novel Transcription Factor, T-bet, Directs Th1 Lineage Commitment

Cell. 2000 Mar 17;100(6):655-69. doi: 10.1016/s0092-8674(00)80702-3.

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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • B-Lymphocytes / physiology
  • Base Sequence
  • Cell Differentiation / immunology
  • Cell Lineage / physiology
  • Cell Polarity / immunology
  • Cloning, Molecular
  • Flow Cytometry
  • Gene Expression / immunology
  • Genes, Reporter
  • Green Fluorescent Proteins
  • Indicators and Reagents / metabolism
  • Interferon-gamma / genetics
  • Interleukin-4 / genetics
  • Interleukin-5 / genetics
  • Killer Cells, Natural / physiology
  • Luminescent Proteins / genetics
  • Mice
  • Mice, Inbred BALB C
  • Mice, Transgenic
  • Molecular Sequence Data
  • Signal Transduction / immunology
  • T-Box Domain Proteins
  • Th1 Cells / chemistry
  • Th1 Cells / cytology*
  • Th1 Cells / immunology
  • Th2 Cells / cytology
  • Th2 Cells / immunology
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism

Substances

  • Indicators and Reagents
  • Interleukin-5
  • Luminescent Proteins
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • Transcription Factors
  • Green Fluorescent Proteins
  • Interleukin-4
  • Interferon-gamma

Associated data

  • GENBANK/AF241242
  • GENBANK/AF241243