Atherosclerotic plaques can remain stable indefinitely, but in some cases the plaque changes abruptly leading to formation of a thrombus or blood clot blocking the coronary artery. Dr. Crea describes the role of T-cell activation in events leading to thrombus formation.

Regardless of the plaque morphology, inflammation is always present at the site of plaque rupture, suggesting a role for inflammation in the destabilisation of fibrous cap tissue (1). Studies by Serneri and colleagues have demonstrated acute T-cell activation in patients with unstable angina (UA) (2), and showed that T-lymphocytes from patients with UA induced the expression of procoagulant activity by monocytes (3). Specifically, lymphocytes of the Th1 phenotype have been shown to induce procoagulant activity and tissue factor production by human monocytes (4).

T-cell mediated induction of tissue factor (and pro-inflammatory cytokine) production has also been observed in human endothelial cells, and this requires cell-to-cell contact between the T-lymphocyte and endothelial cell (5). Activated T-lymphocytes have been found not only in the peri-infarct region but also in remote unaffected regions of the myocardium in patients with recent AMI (6).

Of interest is the CD4+ CD28 null subset of T-lymphocytes, which undergo expansion in patients with UA, suggesting a persistent antigenic stimulation. This subset of T-cells is characterized by enhanced release of IFN-gamma (7). In patients with UA, roughly 50-70% show evidence of inflammation as measured by CRP levels (8), suggesting that other pathways besides inflammation also lead to thrombus formation.

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After viewing this presentation the participant will be able to discuss:

- The effects of activated T-cells on human monocytes and endothelial cells
- T-cell expansion in patients with UA: CD4+ CD28 null subset
- The contribution of inflammation among other pathways leading to thrombus formation

1. AC van der Wal, AE Becker, CM van der Loos and PK Das
Site of intimal rupture or erosion of thrombosed coronary atherosclerotic plaques is characterized by an inflammatory process irrespective of the dominant plaque morphology
Circulation.1994;89:36-44.

2. Gian Gastone Neri Serneri, MD; Domenico Prisco, MD; Francesca Martini, BS; AnnaMaria Gori, BS; Tamara Brunelli, BS; Loredana Poggesi, MD; Carlo Rostagno, MD; Gian Franco Gensini, MD; Rosanna Abbate, MD Acute T-Cell Activation Is Detectable in Unstable Angina Circulation. 1997;95:1806-1812.

3.Serneri GG, Abbate R, Gori AM, Attanasio M, Martini F, Giusti B, Dabizzi P, Poggesi L, Modesti PA, Trotta F, et al.
Transient intermittent lymphocyte activation is responsible for the instability of angina.
Circulation. 1992 Sep;86(3):790-7.

4. G Del Prete, M De Carli, RM Lammel, MM D'Elios, KC Daniel, B Giusti, R Abbate and S Romagnani.
Th1 and Th2 T-helper cells exert opposite regulatory effects on procoagulant activity and tissue factor production by human monocytesBlood.1995;86(1):250-257.

5. Claudia Monaco, Evangelos Andreakos, Sylvia Young, Marc Feldmann and Ewa Paleolog T cell-mediated signaling to vascular endothelium: induction of cytokines, chemokines, and tissue factor Journal of Leukocyte Biology. 2002;71:659-668.

6. Antonio Abbate, MD; Elena Bonanno, MD; Alessandro Mauriello, MD; Rossana Bussani, MD; Giuseppe G.L. Biondi-Zoccai, MD; Giovanna Liuzzo, MD; Antonio Maria Leone, MD; Furio Silvestri, MD; Aldo Dobrina, MD; Feliciano Baldi, MD; Franco Pandolfi, MD; Luigi M. Biasucci, MD; Alfonso Baldi, MD; Luigi G. Spagnoli, MD; Filippo Crea, MD Widespread Myocardial Inflammation and Infarct-Related Artery Patency Circulation. 2004;110:46-50.

7. Giovanna Liuzzo, MD; Stephen L. Kopecky, MD; Robert L. Frye, MD; W. Michael O’ Fallon, PhD; Attilio Maseri, MD; Jorg J. Goronzy, MD; Cornelia M. Weyand, MD Perturbation of the T-Cell Repertoire in Patients With Unstable Angina Circulation. 1999;100:2135.

8. Giovanna Liuzzo, Luigi M. Biasucci, J. Ruth Gallimore, Rita L. Grillo, Antonio G. Rebuzzi, Mark B. Pepys, and Attilio MaseriThe Prognostic Value of C-Reactive Protein and Serum Amyloid A Protein in Severe Unstable AnginaNEJM.1994;331:417-424.