Naive CD8+T Cells Expressing CD95 Increase Human Cardiovascular Disease Severity

Lindsey E. Padgett, Huy Q. Dinh, Runpei Wu, Dalia E. Gaddis, Daniel J. Araujo, Holger Winkels, Anh Nguyen, Coleen A. McNamara, Catherine C. Hedrick

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Objective: Cardiovascular disease (CVD) remains a significant global health concern with a high degree of mortality. While CD4+T cells have been extensively studied in CVD, the importance of CD8+T cells in this disease, despite their abundance and increased activation in human atherosclerotic plaques, remains largely unknown. Thus, the objective of this study was to compare peripheral T-cell signatures between humans with a high (severe) risk of CVD (including myocardial infarction or stroke) and those with a low risk of CVD. Approach and Results: Using mass cytometry, we uncovered a naive CD8+T (TN) cell population expressing CD95 (termed CD95+CD8+stem cell memory T [CD8 TSCM] cells) that was enriched in patients with high compared with low CVD. This T-cell subset enrichment within individuals with high CVD was a relative increase and resulted from the loss of CD95locells within the TNcompartment. We found that CD8 TSCMcells positively correlated with CVD risk in humans, while CD8+TNcells were inversely correlated. Atherosclerotic apolipoprotein E-deficient (ApoE-/-) mice also displayed respective 7-and 2-fold increases in CD8+TSCMfrequencies within the peripheral blood and aorta-draining paraaortic lymph nodes compared with C57BL/6J mice. CD8+TSCMcells were 1.7-fold increased in aortas from western diet fed ApoE-/-mice compared with normal laboratory diet-fed ApoE-/-mice. Importantly, transfer of TSCMcells into immune-deficient Rag.Ldlr recipient mice that lacked T cells increased atherosclerosis, illustrating the importance of these cells in atherogenesis. Conclusions: CD8+TSCMcells are increased in humans with high CVD. As these TSCMcells promote atherosclerosis, targeting them may attenuate atherosclerotic plaque progression.

Original languageEnglish (US)
Pages (from-to)2845-2859
Number of pages15
JournalArteriosclerosis, thrombosis, and vascular biology
StateAccepted/In press - 2020
Externally publishedYes


  • T lymphocytes
  • atherosclerosis
  • cardiovascular diseases
  • mortality
  • myocardial infarction

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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