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The evolving role of T-bet in resistance to infection

Nature Reviews Immunology volume 19, pages 398–410 (2019)Cite this article

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Abstract

The identification of T-bet as a key transcription factor associated with the development of IFNγ-producing CD4+ T cells predicted a crucial role for T-bet in cell-mediated immunity and in resistance to many intracellular infections. This idea was reinforced by initial reports showing that T-bet-deficient mice were more susceptible to pathogens that survived within the lysosomal system of macrophages. However, subsequent studies revealed IFNγ-dependent, T-bet-independent pathways of resistance to diverse classes of microorganisms that occupy other intracellular niches. Consequently, a more complex picture has emerged of how T-bet and the related transcription factor eomesodermin (EOMES) coordinate many facets of the immune response to bona fide pathogens as well as commensals. This article provides an overview of the discovery and evolutionary relationship between T-bet and EOMES and highlights the studies that have uncovered broader functions of T-bet in innate and adaptive immunity and in the development of the effector and memory T cell populations that mediate long-term resistance to infection.

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Fig. 1: The induction and diverse target genes of T-bet.
Fig. 2: Expression of T-bet is linked to T cell trafficking behaviour.
Fig. 3: T-bet in immunity to pathogens that occupy distinct intracellular niches.
Fig. 4: Differential expression and function of T-bet and EOMES during differentiation of effector and memory T cell subsets.

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Acknowledgements

The authors thank S. Reiner for ongoing discussions. Funding support was provided by the National Institutes of Health (NIH) to all authors and the Commonwealth of Pennsylvania to C.A.H.

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Nature Reviews Immunology thanks V. Lazarevic, G. Lord and the other anonymous reviewer(s) for their contribution to the peer review of this work.

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  1. Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Gretchen Harms Pritchard & Christopher A. Hunter

  2. Department of Immunology and Microbiology, School of Medicine, University of Colorado, Aurora, CO, USA

    Ross M. Kedl

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C.A.H. and G.H.P. contributed to researching data, discussion of content and the writing, review and editing of this manuscript. R.M.K. contributed to discussion of content and the review and editing of the manuscript.

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Pritchard, G.H., Kedl, R.M. & Hunter, C.A. The evolving role of T-bet in resistance to infection. Nat Rev Immunol 19, 398–410 (2019). https://doi.org/10.1038/s41577-019-0145-4

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