A novel transcription factor, T-bet, directs Th1 lineage commitment.
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.
Szabo
S J
SJ
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Kim
S T
ST
Costa
G L
GL
Zhang
X
X
Fathman
C G
CG
Glimcher
L H
LH
D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology; D001483:Base Sequence; D002454:Cell Differentiation / Q000276:immunology; D019070:Cell Lineage / Q000502:physiology; D016764:Cell Polarity / Q000276:immunology; D003001:Cloning, Molecular; D005434:Flow Cytometry; D015870:Gene Expression / Q000276:immunology; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D007202:Indicators and Reagents / Q000378:metabolism; D007371:Interferon-gamma / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D015848:Interleukin-5 / Q000235:genetics; D007694:Killer Cells, Natural / Q000502:physiology; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D015398:Signal Transduction / Q000276:immunology; D020825:T-Box Domain Proteins; D018417:Th1 Cells / Q000737:chemistry / Q000166:cytology* / Q000276:immunology; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D000098815:T-bet Transcription Factor
D007202:Indicators and Reagents; D015848:Interleukin-5; D008164:Luminescent Proteins; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D014157:Transcription Factors; D049452:Green Fluorescent Proteins; D015847:Interleukin-4; D007371:Interferon-gamma