Clonally expanded memory CD8+ T cells accumulate in atherosclerotic plaques and are pro-atherogenic in aged mice

Daniel J. Tyrrell*, Kathleen M. Wragg, Judy Chen, Hui Wang, Jianrui Song, Muriel G. Blin, Chase Bolding, Donald Vardaman, Kara Giles, Harrison Tidwell, Md Akkas Ali, Abhinav Janappareddi, Sherri C. Wood, Daniel R. Goldstein

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

Aging is a strong risk factor for atherosclerosis and induces accumulation of memory CD8+ T cells in mice and humans. Biological changes that occur with aging lead to enhanced atherosclerosis, yet the role of aging on CD8+ T cells during atherogenesis is unclear. In this study, using femle mice, we found that depletion of CD8+ T cells attenuated atherogenesis in aged, but not young, animals. Furthermore, adoptive transfer of splenic CD8+ T cells from aged wild-type, but not young wild-type, donor mice significantly enhanced atherosclerosis in recipient mice lacking CD8+ T cells. We also characterized T cells in healthy and atherosclerotic young and aged mice by single-cell RNA sequencing. We found specific subsets of age-associated CD8+ T cells, including a Granzyme K+ effector memory subset, that accumulated and was clonally expanded within atherosclerotic plaques. These had transcriptomic signatures of T cell activation, migration, cytotoxicity and exhaustion. Overall, our study identified memory CD8+ T cells as therapeutic targets for atherosclerosis in aging.

Original languageEnglish
Pages (from-to)1576-1590
Number of pages15
JournalNature Aging
Volume3
Issue number12
DOIs
Publication statusPublished - Dec 2023
Externally publishedYes

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