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  • Review Article
  • Published:

T-bet: a bridge between innate and adaptive immunity

Nature Reviews Immunology volume 13, pages 777–789 (2013)Cite this article

Subjects

Key Points

  • T-bet is expressed in many different cell types of the innate and adaptive immune system in both myeloid and lymphoid lineages.

  • T-bet expression arose early in evolution, before the appearance of the adaptive immune system, which suggests that its function in B cells and T cells may partly reflect coopted transcriptional pathways.

  • T-bet has a crucial role in regulating mucosal homeostasis, mainly via its function in dendritic cells and innate lymphoid cells.

  • T-bet regulates the T helper 1 (TH1) cell differentiation programme by recruiting chromatin-modifying enzymes, which promote permissive chromatin marks at TH1 cell-specific loci by directly regulating the expression of interferon-γ (Ifng) and approximately 27 TH1 cell-specific genes, and by organizing the three-dimensional architecture of the Ifng locus.

  • T-bet blocks the differentiation of other CD4+ TH cell subsets either by inhibiting the expression of TH cell lineage-specifying transcription factors in TH precursor cells or by interfering with their transcriptional activity.

  • T-bet expression in other fully differentiated TH cell subsets results in the acquisition of the TH1 cell phenotype, which may or may not be accompanied by the repression of the existing gene expression profile.

  • During acute infections, T-bet balances terminal differentiation and memory cell potential in both CD4+ and CD8+ T cells. Its expression correlates with the terminal differentiation of CD4+ and CD8+ T effector cells, and its absence correlates with higher memory cell potential.

  • During chronic infections,T-bet expression in CD8+ T cells prevents cell exhaustion.

Abstract

Originally described over a decade ago as a T cell transcription factor regulating T helper 1 cell lineage commitment, T-bet is now recognized as having an important role in many cells of the adaptive and innate immune system. T-bet has a fundamental role in coordinating type 1 immune responses by controlling a network of genetic programmes that regulate the development of certain immune cells and the effector functions of others. Many of these transcriptional networks are conserved across innate and adaptive immune cells and these shared mechanisms highlight the biological functions that are regulated by T-bet.

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Figure 1: Expression and functions of T-bet in immune cells.
Figure 2: T-bet in innate immune cells.
Figure 3: T-bet expression in ILCs and DCs in the intestines.
Figure 4: Role of T-bet in TH1 cell differentiation.
Figure 5: T-bet in the generation of B cell and T cell memory.

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Acknowledgements

We would like to acknowledge support from grants awarded by the US National Institutes of Health (grants CA112663 and PO1NSO38037) to L.H.G.; the Irvington Institute to V.L.; and to G.M.L. the Medical Research Council, UK (grant G0802068), the Wellcome Trust, UK, (grant WT088747MA) and the British Heart Foundation, UK, (grant PG/12/36/29444). G.M.L. is also supported by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy's and St Thomas' National Health Service (NHS) Foundation Trust and King's College London, UK. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.

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Authors and Affiliations

  1. Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, 20892, Maryland, USA

    Vanja Lazarevic

  2. Weill Cornell Medical College, New York, 10065, New York, USA

    Laurie H. Glimcher

  3. Department of Experimental Immunobiology, King's College London, London, SE1 9RT, UK

    Graham M. Lord

Authors
  1. Vanja Lazarevic
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  2. Laurie H. Glimcher
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  3. Graham M. Lord
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Corresponding author

Correspondence to Laurie H. Glimcher.

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Competing interests

L.H.G. is on the Board of Directors and holds equity in Bristol–Myers Squibb, USA.

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Lazarevic, V., Glimcher, L. & Lord, G. T-bet: a bridge between innate and adaptive immunity. Nat Rev Immunol 13, 777–789 (2013). https://doi.org/10.1038/nri3536

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