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Virtual memory T cells develop and mediate bystander protective immunity in an IL-15-dependent manner

Author

Listed:
  • Jason T. White

    (University of Colorado Denver at Anschutz Medical Campus, School of Medicine)

  • Eric W. Cross

    (University of Colorado Denver at Anschutz Medical Campus, School of Medicine)

  • Matthew A. Burchill

    (University of Colorado Denver at Anschutz Medical Campus, School of Medicine)

  • Thomas Danhorn

    (National Jewish Health)

  • Martin D. McCarter

    (University of Colorado Denver at Anschutz Medical Campus, School of Medicine)

  • Hugo R. Rosen

    (University of Colorado Denver at Anschutz Medical Campus, School of Medicine)

  • Brian O’Connor

    (National Jewish Health)

  • Ross M. Kedl

    (University of Colorado Denver at Anschutz Medical Campus, School of Medicine)

Abstract

Virtual memory cells (VM) are an antigen-specific, memory phenotype CD8 T-cell subset found in lymphoreplete, unchallenged mice. Previous studies indicated that VM cells were the result of homeostatic proliferation (HP) resembling the proliferation observed in a lymphopenic environment. Here we demonstrate that HP is ongoing in lymphoreplete mice, the degree of which is dictated by the number of naive CD8 T cells with a sufficiently high affinity for self-antigen interacting with peripheral IL-15. VM cell transcriptional profiles suggest a capacity to mediate protective immunity via antigen non-specific bystander killing, a function we show is dependent on IL-15. Finally, we show a VM-like population of human cells that accumulate with age and traffic to the liver, displaying phenotypic and functional attributes consistent with the bystander protective functions of VM cells identified in the mouse. These data identify developmental and functional attributes of VM cells, including their likely role in protective immunity.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11291
    DOI: 10.1038/ncomms11291
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    Cited by:

    1. Gil-Woo Lee & Young Ju Kim & Sung-Woo Lee & Hee-Ok Kim & Daeun Kim & Jiyoung Kim & You-Me Kim & Keunsoo Kang & Joon Haeng Rhee & Ik Joo Chung & Woo Kyun Bae & In-Jae Oh & Deok Hwan Yang & Jae-Ho Cho, 2024. "Developmental self-reactivity determines pathogenic Tc17 differentiation potential of naive CD8+ T cells in murine models of inflammation," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. Young-Jun Ju & Sung-Woo Lee & Yoon-Chul Kye & Gil-Woo Lee & Hee-Ok Kim & Cheol-Heui Yun & Jae-Ho Cho, 2021. "Self-reactivity controls functional diversity of naive CD8+ T cells by co-opting tonic type I interferon," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    3. 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.

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