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 fo...
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Veröffentlicht in: | Nature aging 2023-12, Vol.3 (12), p.1576-1590 |
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Sprache: | eng |
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Zusammenfassung: | 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. |
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ISSN: | 2662-8465 2662-8465 |
DOI: | 10.1038/s43587-023-00515-w |