颗粒酶B
细胞毒性T细胞
CD8型
过继性细胞移植
生物
免疫学
颗粒酶
白细胞介素21
T细胞
穿孔素
免疫系统
细胞生物学
体外
生物化学
作者
Daniel J. Tyrrell,Kathleen M Wragg,Judy Chen,Hui Wang,Jianrui Song,Muriel G. Blin,Chase Bolding,Donald Vardaman,Katherine M. Giles,Harrison Tidwell,Md Akkas Ali,Abhinav Janappareddi,Sherri C. Wood,Daniel R. Goldstein
出处
期刊:Nature Aging
日期:2023-11-23
卷期号:3 (12): 1576-1590
被引量:1
标识
DOI:10.1038/s43587-023-00515-w
摘要
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.
科研通智能强力驱动
Strongly Powered by AbleSci AI