TY - JOUR
T1 - Clonally expanded memory CD8+ T cells accumulate in atherosclerotic plaques and are pro-atherogenic in aged mice
AU - Tyrrell, Daniel J.
AU - Wragg, Kathleen M.
AU - Chen, Judy
AU - Wang, Hui
AU - Song, Jianrui
AU - Blin, Muriel G.
AU - Bolding, Chase
AU - Vardaman, Donald
AU - Giles, Kara
AU - Tidwell, Harrison
AU - Ali, Md Akkas
AU - Janappareddi, Abhinav
AU - Wood, Sherri C.
AU - Goldstein, Daniel R.
N1 - Publisher Copyright:
© 2023, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85177637240&partnerID=8YFLogxK
U2 - 10.1038/s43587-023-00515-w
DO - 10.1038/s43587-023-00515-w
M3 - Article
AN - SCOPUS:85177637240
SN - 2662-8465
VL - 3
SP - 1576
EP - 1590
JO - Nature Aging
JF - Nature Aging
IS - 12
ER -