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Quantifiable blood TCR repertoire components associate with immune aging

Author

Listed:
  • Jing Hu

    (University of Pennsylvania
    Children’s Hospital of Philadelphia)

  • Mingyao Pan

    (University of Pennsylvania)

  • Brett Reid

    (Moffitt Cancer Center)

  • Shelley Tworoger

    (Moffitt Cancer Center
    Oregon Health and Science University)

  • Bo Li

    (University of Pennsylvania
    Children’s Hospital of Philadelphia)

Abstract

T cell senescence alters the homeostasis of distinct T cell populations and results in decayed adaptive immune protection in older individuals, but a link between aging and dynamic T cell clone changes has not been made. Here, using a newly developed computational framework, Repertoire Functional Units (RFU), we investigate over 6500 publicly available TCR repertoire sequencing samples from multiple human cohorts and identify age-associated RFUs consistently across different cohorts. Quantification of RFU reduction with aging reveals accelerated loss under immunosuppressive conditions. Systematic analysis of age-associated RFUs in clinical samples manifests a potential link between these RFUs and improved clinical outcomes, such as lower ICU admission and reduced risk of complications, during acute viral infections. Finally, patients receiving bone marrow transplantation show a secondary expansion of the age-associated clones upon stem cell transfer from younger donors. Together, our results suggest the existence of a ‘TCR clock’ that could reflect the immune functions in aging populations.

Suggested Citation

  • Jing Hu & Mingyao Pan & Brett Reid & Shelley Tworoger & Bo Li, 2024. "Quantifiable blood TCR repertoire components associate with immune aging," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52522-z
    DOI: 10.1038/s41467-024-52522-z
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    References listed on IDEAS

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    1. Bonnie van Wilgenburg & Iris Scherwitzl & Edward C. Hutchinson & Tianqi Leng & Ayako Kurioka & Corinna Kulicke & Catherine de Lara & Suzanne Cole & Sirijitt Vasanawathana & Wannee Limpitikul & Prida M, 2016. "MAIT cells are activated during human viral infections," Nature Communications, Nature, vol. 7(1), pages 1-11, September.
    2. Cecily Choy & Joseph Chen & Jiangyuan Li & D. Travis Gallagher & Jian Lu & Daichao Wu & Ainslee Zou & Humza Hemani & Beverly A. Baptiste & Emily Wichmann & Qian Yang & Jeffrey Ciffelo & Rui Yin & Juli, 2023. "SARS-CoV-2 infection establishes a stable and age-independent CD8+ T cell response against a dominant nucleocapsid epitope using restricted T cell receptors," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    3. Pradyot Dash & Andrew J. Fiore-Gartland & Tomer Hertz & George C. Wang & Shalini Sharma & Aisha Souquette & Jeremy Chase Crawford & E. Bridie Clemens & Thi H. O. Nguyen & Katherine Kedzierska & Nicole, 2017. "Quantifiable predictive features define epitope-specific T cell receptor repertoires," Nature, Nature, vol. 547(7661), pages 89-93, July.
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