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, yet the role of aging on CD8+ T cells during atherogenesis is unclear. Here we found that depletion of CD8+ T cells attenuated atherogenesis in aged, but not young mice. Furthermore, adoptive transfer of splenic CD8+ T cells, which contain a high proportion of memory T cells, from aged wild-type, but not young wild-type donors, significantly enhanced atherosclerosis in Cd8-/- recipient mice. Thus, we characterized T cells in healthy and atherosclerotic young and aged mice by single-cell RNA-sequencing. We found that with aging effector memory, central memory, and granzyme K+ effector memory CD8+ T cells accumulate and are clonally expanded within atherosclerotic plaques and aging altered transcriptomic profiles related to CD8+ T cell activation, migration, cytotoxicity, and exhaustion. Overall, our study identifies memory CD8+ T cells as potential therapeutic targets for reducing atherosclerosis in older adults.