ArticleAmerican journal of physiology. Heart and circulatory physiology2019
Direct CD137 costimulation of CD8 T cells promotes retention and innate-like function within nascent atherogenic foci.
Article in American journal of physiology. Heart and circulatory physiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
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The trial behind it
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Who cites it
10 citing papers in PubMed, 13 citations in OpenAlex.
- Screening of atherosclerosis diagnostic markers based on lymphangiogenesis-related genes and analysis of immunological characteristics.Journal of cardiothoracic surgery · 2026Article
- Endothelial Elavl1 Is Required for CD8 T-Cell Persistence in Atherosclerosis.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Progenitor exhausted PD-1Nature cardiovascular research · 2025Article
- TNF superfamily molecules in atherosclerosis: mechanistic insights and therapeutic translation.Frontiers in immunology · 2025Review
- Endothelial Immunosuppression in Atherosclerosis : Translational Control by Elavl1/HuR.bioRxiv : the preprint server for biology · 2024Article
- Optimal CD8Nature communications · 2022Article
- CD8Cells · 2020Review
- Adaptive immunity-driven inflammation and cardiovascular disease.American journal of physiology. Heart and circulatory physiology · 2019Review
- The Progress of Investigating the CD137-CD137L Axis as a Potential Target for Systemic Lupus Erythematosus.Cells · 2019Review
- Activated T-effector seeds: cultivating atherosclerotic plaque through alternative activation.American journal of physiology. Heart and circulatory physiology · 2019Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Effector CD8 T cells infiltrate atherosclerotic lesions and are correlated with cardiovascular events, but the mechanisms regulating their recruitment and retention are not well understood. CD137 (4-1BB) is a costimulatory receptor induced on immune cells and expressed at sites of human atherosclerotic plaque. Genetic variants associated with decreased CD137 expression correlate with carotid-intimal thickness and its deficiency in animal models attenuates atherosclerosis. These effects have been attributed in part to endothelial responses to low and disturbed flow (LDF), but CD137 also generates robust effector CD8 T cells as a costimulatory signal. Thus, we asked whether CD8 T cell-specific CD137 stimulation contributes to their infiltration, retention, and IFNγ production in early atherogenesis. We tested this through adoptive transfer of CD8 T cells into recipient C57BL/6J mice that were then antigen primed and CD137 costimulated. We analyzed atherogenic LDF vessels in normolipidemic and PCSK9-mediated hyperlipidemic models and utilized a digestion protocol that allowed for lesional T-cell characterization via flow cytometry and in vitro stimulation. We found that CD137 activation, specifically of effector CD8 T cells, triggers their intimal infiltration into LDF vessels and promotes a persistent innate-like proinflammatory program. Residence of CD137
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.