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Interferon-γ couples CD8+ T cell avidity and differentiation during infection

Author

Listed:
  • Lion F. K. Uhl

    (University of Oxford)

  • Han Cai

    (University of Oxford)

  • Sophia L. Oram

    (University of Oxford)

  • Jagdish N. Mahale

    (University of Oxford)

  • Andrew J. MacLean

    (University of Oxford)

  • Julie M. Mazet

    (University of Oxford)

  • Theo Piccirilli

    (University of Oxford)

  • Alexander J. He

    (University of Oxford)

  • Doreen Lau

    (University of Oxford)

  • Tim Elliott

    (University of Oxford)

  • Audrey Gerard

    (University of Oxford)

Abstract

Effective responses to intracellular pathogens are characterized by T cell clones with a broad affinity range for their cognate peptide and diverse functional phenotypes. How T cell clones are selected throughout the response to retain a breadth of avidities remains unclear. Here, we demonstrate that direct sensing of the cytokine IFN-γ by CD8+ T cells coordinates avidity and differentiation during infection. IFN-γ promotes the expansion of low-avidity T cells, allowing them to overcome the selective advantage of high-avidity T cells, whilst reinforcing high-avidity T cell entry into the memory pool, thus reducing the average avidity of the primary response and increasing that of the memory response. IFN-γ in this context is mainly provided by virtual memory T cells, an antigen-inexperienced subset with memory features. Overall, we propose that IFN-γ and virtual memory T cells fulfil a critical immunoregulatory role by enabling the coordination of T cell avidity and fate.

Suggested Citation

  • Lion F. K. Uhl & Han Cai & Sophia L. Oram & Jagdish N. Mahale & Andrew J. MacLean & Julie M. Mazet & Theo Piccirilli & Alexander J. He & Doreen Lau & Tim Elliott & Audrey Gerard, 2023. "Interferon-γ couples CD8+ T cell avidity and differentiation during infection," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42455-4
    DOI: 10.1038/s41467-023-42455-4
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    References listed on IDEAS

    as
    1. Dietmar Zehn & Sarah Y. Lee & Michael J. Bevan, 2009. "Complete but curtailed T-cell response to very low-affinity antigen," Nature, Nature, vol. 458(7235), pages 211-214, March.
    2. Jason T. White & Eric W. Cross & Matthew A. Burchill & Thomas Danhorn & Martin D. McCarter & Hugo R. Rosen & Brian O’Connor & Ross M. Kedl, 2016. "Virtual memory T cells develop and mediate bystander protective immunity in an IL-15-dependent manner," Nature Communications, Nature, vol. 7(1), pages 1-13, September.
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