Effector memory T cells are associated with atherosclerosis in humans and animal models

Enrico Ammirati, Domenico Cianflone, Viviana Vecchio, Michela Banfi, Anna C. Vermi, Monica De Metrio, Liliana Grigore, Fabio Pellegatta, Angela Pirillo, Katia Garlaschelli, Angelo A. Manfredi, Alberico L. Catapano, Attilio Maseri, Alessio G. Palini, Giuseppe D. Norata

Research output: Contribution to journalArticle

Abstract

Background- Adaptive T-cell response is promoted during atherogenesis and results in the differentiation of näive CD4+T cells to effector and/or memory cells of specialized T-cell subsets. Aim of this work was to investigate the relationship between circulating CD4+T-cell subsets and atherosclerosis. Methods and Results- We analyzed 57 subsets of circulating CD4+T cells by 10-parameter/8-color polychromatic flow cytometry (markers: CD3/CD4/CD45RO/CD45RA/CCR7/CCR5/CXCR3/HLA-DR) in peripheral blood from 313 subjects derived from 2 independent cohorts. In the first cohort of subjects from a free-living population (n=183), effector memory T cells (TEM: CD3+CD4+CD45RA-CD45RO+CCR7- cells) were strongly related with intima-media thickness of the common carotid artery, even after adjustment for age (r=0.27; P<0.001). Of note, a significant correlation between TEM and low-density lipoproteins was observed. In the second cohort (n=130), TEM levels were significantly increased in patients with chronic stable angina or acute myocardial infarction compared with controls. HLA-DR+TEM were the TEM subpopulation with the strongest association with the atherosclerotic process (r=0.37; P<0.01). Finally, in animal models of atherosclerosis, TEM (identified as CD4+CD44+CD62L-) were significantly increased in low-density lipoprotein receptor and apolipoprotein E deficient mice compared with controls and were correlated with the extent of atherosclerotic lesions in the aortic root (r=0.56; P<0.01). Conclusions- Circulating TEM cells are associated with increased atherosclerosis and coronary artery disease in humans and in animal models and could represent a key CD4+T-cell subset related to the atherosclerotic process.

Original languageEnglish
Pages (from-to)27-41
Number of pages15
JournalJournal of the American Heart Association
Volume1
Issue number1
DOIs
Publication statusPublished - 2012

Keywords

  • Atherosclerosis
  • C-c chemokine receptor type 7
  • Chemokines
  • Coronary artery disease
  • Effector memory t cells

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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  • Cite this

    Ammirati, E., Cianflone, D., Vecchio, V., Banfi, M., Vermi, A. C., De Metrio, M., Grigore, L., Pellegatta, F., Pirillo, A., Garlaschelli, K., Manfredi, A. A., Catapano, A. L., Maseri, A., Palini, A. G., & Norata, G. D. (2012). Effector memory T cells are associated with atherosclerosis in humans and animal models. Journal of the American Heart Association, 1(1), 27-41. https://doi.org/10.1161/JAHA.111.000125