Altered CD31 expression and activity in helper T cells of acute coronary syndrome patients

Davide Flego, Anna Severino, Francesco Trotta, Marco Previtero, Sara Ucci, Chiara Zara, Daniela Pedicino, Gianluca Massaro, Luigi M. Biasucci, Giovanna Liuzzo, Filippo Crea

Research output: Contribution to journalArticle

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+CD28null (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+CD28null 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.

Original languageEnglish
JournalBasic Research in Cardiology
Volume109
Issue number6
DOIs
Publication statusPublished - 2014

Keywords

  • Acute coronary syndromes
  • CD31
  • Immune system
  • Signaling pathways
  • T cells

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)
  • Physiology
  • Medicine(all)

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    Flego, D., Severino, A., Trotta, F., Previtero, M., Ucci, S., Zara, C., Pedicino, D., Massaro, G., Biasucci, L. M., Liuzzo, G., & Crea, F. (2014). Altered CD31 expression and activity in helper T cells of acute coronary syndrome patients. Basic Research in Cardiology, 109(6). https://doi.org/10.1007/s00395-014-0448-3