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

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.