A novel transcription factor, T-bet, directs Th1 lineage commitment.

By S. Szabo, Sean T. Kim, G. Costa, Xiankui Zhang, C. Fathman, L. Glimcher. Cell, 2000

3,870 citations recorded by the source corpus.

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.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/4031ede83b3cb707ca0bff914d4e2e288827dd73

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

1. W. E. Paul
2. D. Cua
3. Jinfang Zhu
4. Dan R. Littman
5. V. Kuchroo
6. R. Flavell
7. F. Sallusto
8. A. Lanzavecchia

Citations in the corpus

• Syk- and CARD9-dependent coupling of innate immunity to the induction of T helper cells that produce interleukin 17 (2007, background): “These cytokines act on newly primed CD4 + T cells to induce expression of the transcription factor T-bet, which promotes T H 1 response”
• Diversification of haematopoietic stem cells to specific lineages (2000, background): “cgi?l=30009"> T-bet , which is normally expressed specifically within T H 1 cells, can, when expressed in T H 2 cells, convert them into T H 1 cell”
• Phenotypic and functional specialization of FOXP3+ regulatory T cells (2011, background): “The functional specialization of these various CD4 + T cell subsets is due to the differential expression of 'master' transcription factors, namely retinoic acid receptor-related orphan receptor-γt (RORγt), T-bet and GATA-binding protein 3 (GATA3), which turn on distinct programmes of gene expressi”
• Global mapping of H3K4me3 and H3K27me3 reveals specificity and plasticity in lineage fate determination of differentiating CD4+ T cells. (2009, background): “…and activator of transcription 4 (Stat4), initiates the development of Th1 cells that produce the signature cytokine interferon-g (IFN-g) and express the key regulator T-box 21 (Tbx21, also called T-bet) (Afkarian et al., 2002; Kaplan et al., 1996b; Szabo et al., 2000; Thierfelder et al., 1996).”
• Production of interleukin 22 but not interleukin 17 by a subset of human skin-homing memory T cells (2009, background): “T helper type 1 (T H 1) differentiation is promoted by interleukin 12 (IL-12) and requires the lineage-specifying transcription factor T-bet, whereas T H 2 differentiation is promoted by IL-4 and is dependent on expression of the transcription factor GATA-3 (refs”