Basic Research in Cardiology

, 109:448 | Cite as

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
Original Contribution

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.

Keywords

Acute coronary syndromes Signaling pathways Immune system T cells CD31 

Supplementary material

395_2014_448_MOESM1_ESM.docx (407 kb)
Supplementary material 1 (DOCX 406 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Davide Flego
    • 1
  • Anna Severino
    • 1
  • Francesco Trotta
    • 1
  • Marco Previtero
    • 1
  • Sara Ucci
    • 1
  • Chiara Zara
    • 1
  • Daniela Pedicino
    • 1
  • Gianluca Massaro
    • 1
  • Luigi M. Biasucci
    • 1
  • Giovanna Liuzzo
    • 1
  • Filippo Crea
    • 1
  1. 1.Institute of CardiologyCatholic UniversityRomeItaly

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