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.

Flego, D., Severino, A., Trotta, F., Previtero, M., Ucci, S., Zara, C., Pedicino, D., Massaro, G., Biasucci, L. M., Liuzzo, G., Crea, F., Altered CD31 expression and activity in helper T cells of acute coronary syndrome patients, <<BASIC RESEARCH IN CARDIOLOGY>>, 2014; 109 (6): 448-448. [doi:10.1007/s00395-014-0448-3] [http://hdl.handle.net/10807/60757]

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

Flego, Davide;Severino, Anna;Trotta, Francesco;Ucci, Sarassunta;Zara, Chiara;Pedicino, Daniela;Biasucci, Luigi Marzio;Liuzzo, Giovanna;Crea, Filippo
2014

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.
2014
Inglese
Flego, D., Severino, A., Trotta, F., Previtero, M., Ucci, S., Zara, C., Pedicino, D., Massaro, G., Biasucci, L. M., Liuzzo, G., Crea, F., Altered CD31 expression and activity in helper T cells of acute coronary syndrome patients, <<BASIC RESEARCH IN CARDIOLOGY>>, 2014; 109 (6): 448-448. [doi:10.1007/s00395-014-0448-3] [http://hdl.handle.net/10807/60757]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/60757
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