Platelets from Patients with Myocardial Infarction Can Activate T Cells in Vitro

Specific aim: Our aim was to examine whether T cells can be activated by the circulating activated platelets from patients with myocardial infarction (with ST elevation-STEMI)

Methods: After written informed consent was obtained, peripheral blood mononuclear cells (PBMCs) were isolated from heparinized venous blood obtained from 20 patients with STEMI (18 men and 2 women) at the time of hospital admission at diagnosis, before receiving any treatment, as well as 5 days and 30 days later.  We also analyzed 10 healthy subjects (8 men and 2 women), and 5 patients with unstable angina who served as the disease control group.  PBMCs were analyzed by flow cytometry with the following markers and their isotypic controls: CD4, CD25, CD69, and FOXP3. We also isolated platelet rich plasma or plasma alone from the patients and the healthy subjects, and used in mixed cultures with PBMCs.

Results: We first examined T cell activation by measuring CD69 expression on CD4 T cells following incubation with platelets obtained from patients with STEMI. T cells treated with platelets from patients with STEMI showed increased expression of CD69 (as an activation marker) compared with T cells treated with platelets from healthy subjects (p<0.05, Figure 1). There was no T cell activation following incubation with plasma alone from patients or healthy controls.

We then examined the percentages of CD4+CD25+hi (regulatory T cells). There was no statistical difference in Tregs between patients at presentation and controls (healthy subjects and disease control group).  Five days later, patients with STEMI displayed increased levels of Tregs compared with the 2 control groups; one month later, Treg numbers returned to the initial presentation levels (p<0.05, Figure 2)

Conclusion:  To our knowledge we describe for the first time that platelets from patients with STEMI can activate T cells in vitro. In patients with STEMI, an increase in Tregs possibly in an effort to suppress immune system activation secondary to platelet activation, appears shortly after the infarct and normalizes a month later.

Figure 1: T cell activation after treatment with platelets from patients with STEMI compared with the platelets from healthy controls or plasma alone

Figure 2:  Increased T regs in patients with STEMI , 5 days after admission (STEMI EXIT) ( UA;unstable angina, STEMI 1mfup; STEMI after one month)

Figure 1 

Figure 2