Quantifiable blood TCR repertoire components associate with immune aging

Jing Hu, Mingyao Pan, Brett Reid, Shelley Tworoger and Bo Li ()
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Jing Hu: University of Pennsylvania
Mingyao Pan: University of Pennsylvania
Brett Reid: Moffitt Cancer Center
Shelley Tworoger: Moffitt Cancer Center
Bo Li: University of Pennsylvania

Nature Communications, 2024, vol. 15, issue 1, 1-13

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-52522-z

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