Effector Memory T cells Are Associated With Atherosclerosis in Humans and Animal Models

Abstract

Background Adaptive T‐cell response is promoted during atherogenesis and results in the differentiation of naïve 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 (T EM : 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 T EM and low‐density lipoproteins was observed. In the second cohort ( n =130), T EM levels were significantly increased in patients with chronic stable angina or acute myocardial infarction compared with controls. HLA‐DR + T EM were the T EM subpopulation with the strongest association with the atherosclerotic process ( r =0.37; P <0.01). Finally, in animal models of atherosclerosis, T EM (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 T EM 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. ( J Am Heart Assoc 2012;1:27‐41.)