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.)