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Antigen specificity shapes distinct aging trajectories of memory CD8⁺ T cells

Author

Listed:
  • Ines Sturmlechner

    (Mayo Clinic
    Mayo Clinic)

  • Abhinav Jain

    (Mayo Clinic)

  • Bin Hu

    (Stanford University
    Palo Alto Veterans Administration Healthcare System)

  • Rohit R. Jadhav

    (Mayo Clinic
    Stanford University
    Palo Alto Veterans Administration Healthcare System)

  • Wenqiang Cao

    (Mayo Clinic
    Stanford University
    Palo Alto Veterans Administration Healthcare System
    Health Sciences Institute of China Medical University)

  • Hirohisa Okuyama

    (Mayo Clinic)

  • Lu Tian

    (Stanford University)

  • Cornelia M. Weyand

    (Mayo Clinic
    Stanford University
    Mayo Clinic)

  • Jörg J. Goronzy

    (Mayo Clinic
    Mayo Clinic
    Stanford University
    Palo Alto Veterans Administration Healthcare System)

Abstract

Memory T cells are a highly heterogeneous collection of antigen-experienced cells that undergo dynamic adaptations upon antigen re-encounter and environmental signals. This heterogeneity hinders studies on memory T cell durability and age-related dysfunction. Using chronic Epstein-Barr virus (EBV) infection and barcode-enabled antigen tracing, we assess the influence of age on memory states at the level of single antigen-specific CD8+ T cells. In young adults ( 65-years), antigen-specific cells show largely distinct phenotypic and transcriptomic aging trajectories. Common to many albeit not all antigen-specific populations are maintained TCR diversity, gained natural killer cell-like, innate signatures and lost stem-like features while no evidence is seen for cellular senescence or exhaustion. TCR avidity contributes to these phenotypic differences and aging-related changes. Collectively, our data uncover divergent antigen-guided aging shifts in memory T cell phenotypes, which are informative for antigen selection in optimizing vaccine design and adoptive T cell therapy.

Suggested Citation

  • Ines Sturmlechner & Abhinav Jain & Bin Hu & Rohit R. Jadhav & Wenqiang Cao & Hirohisa Okuyama & Lu Tian & Cornelia M. Weyand & Jörg J. Goronzy, 2025. "Antigen specificity shapes distinct aging trajectories of memory CD8⁺ T cells," Nature Communications, Nature, vol. 16(1), pages 1-21, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-61627-y
    DOI: 10.1038/s41467-025-61627-y
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