title: Effector Memory T cells Are Associated With Atherosclerosis in Humans and Animal Models.
abstract: BACKGROUND#ENTITYSTARTX02014;: 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#ENTITYSTARTX02014;: 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#ENTITYSTARTX02014;: 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.).
authors.affiliation: Clinical Cardiovascular Biology Centre, San Raffaele Scientific Institute and the Università Vita-Salute San Raffaele , Milan, Italy (E.A., D.C., M.B.) ; Heart Transplantation Division, Ospedale Niguarda Ca' Granda , Milan, Italy (E.A.) ; Heart Care Foundation , Florence, Italy (E.A., A.M.).
authors.forename: Enrico
authors.initials: E
authors.lastname: Ammirati
authors.forename: Domenico
authors.initials: D
authors.lastname: Cianflone
authors.forename: Viviana
authors.initials: V
authors.lastname: Vecchio
authors.forename: Michela
authors.initials: M
authors.lastname: Banfi
authors.forename: Anna C
authors.initials: AC
authors.lastname: Vermi
authors.forename: Monica
authors.initials: M
authors.lastname: De Metrio
authors.forename: Liliana
authors.initials: L
authors.lastname: Grigore
authors.forename: Fabio
authors.initials: F
authors.lastname: Pellegatta
authors.forename: Angela
authors.initials: A
authors.lastname: Pirillo
authors.forename: Katia
authors.initials: K
authors.lastname: Garlaschelli
authors.forename: Angelo A
authors.initials: AA
authors.lastname: Manfredi
authors.forename: Alberico L
authors.initials: AL
authors.lastname: Catapano
authors.forename: Attilio
authors.initials: A
authors.lastname: Maseri
authors.forename: Alessio G
authors.initials: AG
authors.lastname: Palini
authors.forename: Giuseppe D
authors.initials: GD
authors.lastname: Norata
keywords: C-c chemokine receptor type 7; atherosclerosis; chemokines; coronary artery disease; effector memory T cells