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

Autor: Tyrrell DJ; Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA. danieltyrrell@uabmc.edu.; Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA. danieltyrrell@uabmc.edu., Wragg KM; Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA., Chen J; Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.; Program in Immunology, University of Michigan, Ann Arbor, MI, USA., Wang H; Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA., Song J; Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA., Blin MG; Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA., Bolding C; Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA., Vardaman D 3rd; Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA., Giles K; Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA., Tidwell H; Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA., Ali MA; Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA., Janappareddi A; Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA., Wood SC; Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA., Goldstein DR; Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.; Program in Immunology, University of Michigan, Ann Arbor, MI, USA.; Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI, USA.
Jazyk: angličtina
Zdroj: Nature aging [Nat Aging] 2023 Dec; Vol. 3 (12), pp. 1576-1590. Date of Electronic Publication: 2023 Nov 23.
DOI: 10.1038/s43587-023-00515-w
Abstrakt: 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.
(© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze: MEDLINE
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