title: Altered CD31 expression and activity in helper T cells of acute coronary syndrome patients.
abstract: In acute coronary syndrome (ACS), T cell abnormalities are associated to a worse outcome. Loss of inhibitory activity of CD31, an Ig-like adhesion molecule, on peripheral leukocytes has been found to enhance atherosclerosis in experimental models. In this study, we examined the expression of CD31 on T cells, and its role on TCR signaling in 35 patients with non-ST elevation ACS, in 35 patients with stable angina (SA), and in 35 controls. Furthermore, 10 ACS and 10 SA patients were re-analyzed at 1-year follow-up. Flow-cytometry analysis showed that in ACS patients, CD31 expression was reduced on total CD4(+) and CD4(+)CD28(null) (P < 0.001, ACS vs. SA), on naïve (P < 0.001, ACS vs. SA) and on central-memory and effector-memory CD4(+) T cells (P < 0.05, ACS vs. SA and controls). The immunomodulatory effect of CD31 on TCR signaling of CD4(+) and CD4(+)CD28(null) T cells, was lower in ACS than SA patients (P < 0.05, for both comparisons). At 1-year follow-up, CD31 expression and function increased in ACS becoming similar to that found in SA. CD31 recruitment in the immunological synapse was lower in ACS than controls (P = 0.012). Moreover, CD31 modulated MAPK signaling and reduced the expression of T bet and Rorγ-t, necessary for Th1 and Th17 differentiation. Finally, we studied TCR signaling in CD31(+) naïve and primed T cell subsets observing a different pattern of protein phosphorylation. A CD31-mediated regulatory pathway is enhanced in SA and temporarily downregulated in ACS. As CD31 modulates both T cell activation, by increasing the threshold for TCR stimulation, and T cell differentiation, it might represent a novel molecular target to treat T cell abnormalities in ACS.
authors.affiliation: Institute of Cardiology, Catholic University, Largo A. Gemelli, 8, 00168, Rome, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Flego
authors.forename: Anna
authors.initials: A
authors.lastname: Severino
authors.forename: Francesco
authors.initials: F
authors.lastname: Trotta
authors.forename: Marco
authors.initials: M
authors.lastname: Previtero
authors.forename: Sara
authors.initials: S
authors.lastname: Ucci
authors.forename: Chiara
authors.initials: C
authors.lastname: Zara
authors.forename: Daniela
authors.initials: D
authors.lastname: Pedicino
authors.forename: Gianluca
authors.initials: G
authors.lastname: Massaro
authors.forename: Luigi M
authors.initials: LM
authors.lastname: Biasucci
authors.forename: Giovanna
authors.initials: G
authors.lastname: Liuzzo
authors.forename: Filippo
authors.initials: F
authors.lastname: Crea
mesh_terms: D054058:Acute Coronary Syndrome / Q000276:immunology* / Q000378:metabolism; D000368:Aged; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000502:physiology*; D011446:Prospective Studies; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology*
chemical_list: D019408:Platelet Endothelial Cell Adhesion Molecule-1