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Infection-induced type I interferons critically modulate the homeostasis and function of CD8+ naïve T cells

Author

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  • Mladen Jergović

    (University of Arizona College of Medicine)

  • Christopher P. Coplen

    (University of Arizona College of Medicine)

  • Jennifer L. Uhrlaub

    (University of Arizona College of Medicine)

  • David G. Besselsen

    (University Animal Care, University of Arizona)

  • Shu Cheng

    (University of Arizona College of Medicine)

  • Megan J. Smithey

    (University of Arizona College of Medicine
    Vir, Inc.)

  • Janko Nikolich-Žugich

    (University of Arizona College of Medicine)

Abstract

Naïve T (Tn) cells require two homeostatic signals for long-term survival: tonic T cell receptor:self-peptide–MHC contact and IL-7 stimulation. However, how microbial exposure impacts Tn homeostasis is still unclear. Here we show that infections can lead to the expansion of a subpopulation of long-lived, Ly6C+ CD8+ Tn cells with accelerated effector function. Mechanistically, mono-infection with West Nile virus transiently, and polymicrobial exposure persistently, enhances Ly6C expression selectively on CD5hiCD8+ cells, which in the case of polyinfection translates into a numerical CD8+ Tn cell increase in the lymph nodes. This conversion and expansion of Ly6C+ Tn cells depends on IFN-I, which upregulates MHC class I expression and enhances tonic TCR signaling in differentiating Tn cells. Moreover, for Ly6C+CD8+ Tn cells, IFN-I-mediated signals optimize their homing to secondary sites, extend their lifespan, and enhance their effector differentiation and antibacterial function, particularly for low-affinity clones. Our results thus uncover significant regulation of Tn homeostasis and function via infection-driven IFN-I, with potential implications for immunotherapy.

Suggested Citation

  • Mladen Jergović & Christopher P. Coplen & Jennifer L. Uhrlaub & David G. Besselsen & Shu Cheng & Megan J. Smithey & Janko Nikolich-Žugich, 2021. "Infection-induced type I interferons critically modulate the homeostasis and function of CD8+ naïve T cells," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25645-w
    DOI: 10.1038/s41467-021-25645-w
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    Cited by:

    1. Jolene S. Ranek & Wayne Stallaert & J. Justin Milner & Margaret Redick & Samuel C. Wolff & Adriana S. Beltran & Natalie Stanley & Jeremy E. Purvis, 2024. "DELVE: feature selection for preserving biological trajectories in single-cell data," Nature Communications, Nature, vol. 15(1), pages 1-26, December.

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