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BATF targets T cell exhaustion for termination

Nature Immunology volume 22, pages 936–938 (2021)Cite this article

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New reports provide further insight into the role of the transcription factor BATF in pivoting the differentiation of CD8+ T cells away from T cell exhaustion and facilitating the transition of these cells into potent effectors.

Recent work has demonstrated that the pool of exhausted T cells is heterogeneous, with several distinct subtypes of T cells represented in various developmental states. Specifically, the pool was previously thought to comprise terminally exhausted CD8+ T cells, which predominantly express high amounts of inhibitory receptors and display poor proliferative potential in conjunction with impaired cytotoxic capacity. Nuanced work has now revealed that the pool also contains a relatively small population of exhausted progenitor T cells, marked by an enriched “stem-like” signature. More recently, a population of CX3CR1+ effector T cells4,5 has been described, which may represent a transitory population (Fig. 1). However, whether this heterogeneity represents a developmental spectrum and what the specific determinants regulating these processes are remain active areas of investigation. Moreover, discovering regulatory processes that control or mediate this transition may provide new avenues for improving cell-based therapeutics.

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Fig. 1: BATF regulates T cell subset specification.

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Acknowledgements

This work was supported by the National Institutes of Health R01AI114442 and R01CA237311 to B.Y. and F32CA250155-01A1 to S.K.B. and by the American Lebanese Syrian Associated Charities (ALSAC) to B.Y. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Authors and Affiliations

  1. Department of Immunology, St. Jude Children’s Research Hospital, Memphis, TN, USA

    Shannon K. Boi, Xin Lan & Ben Youngblood

  2. College of Graduate Health Sciences, University of Tennessee Health Science Center, Memphis, TN, USA

    Xin Lan

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  1. Shannon K. Boi
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Correspondence to Ben Youngblood.

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Competing interests

B.Y. has patents related to epigenetic biomarkers and methods for enhancing CAR T cell function. S.K.B. and X.L. declare no competing interests.

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Boi, S.K., Lan, X. & Youngblood, B. BATF targets T cell exhaustion for termination. Nat Immunol 22, 936–938 (2021). https://doi.org/10.1038/s41590-021-00978-2

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