Vascular effects of circulating CD4-T cells in patients with unstable angina

T cells are involved in the process of endothelial dysfunction contributing to plaque destabilization [1] and several studies have shown that the predominant population of T cells that infiltrates atherosclerotic plaques is CD4+ T cells [2]. An increased number of CD4+ T cells have already been found in the peripheral blood of patients presenting with acute coronary syndromes [3]. Particularly, a subset of CD4+ T cells characterized by a loss of the CD31 molecule seems to have a crucial role in plaque destabilization and thrombotic complications. Furthermore, an increased number of CD4+ T lymphocytes characterized by a defective cell surface expression of CD28 have been detected in patients with unstable angina (UA). CD4+CD28null T cells were found to expand in the peripheral blood of patients with UA and infiltrate unstable coronary plaques, where they undergo clonal expansion, probably due to their activation by specific antigens [4]. Therefore, we aimed to investigate whether CD4+CD31null and CD4+CD28null T cell subpopulations contribute to vascular function in patients with UA. We enrolled 61 patients with UA admitted to our Coronary Care Unit with UA Braunwald's class IIIB and 23 healthy individuals without overt cardiovascular disease who were screened in our outpatients' clinic for cardiovascular prevention. Endothelial function was evaluated by estimating the flow-mediated dilation (FMD) in the brachial artery, while flow cytometry was used to determine both the number of T-cells present as well as the frequencies of the various T-cell subsets of interest. We have found that endothelial function was significantly impaired in patients with UA compared to healthy controls (4.76 ± 0.24 vs 8.4 ±0.52, p b 0.001, Fig. 1A), while further analysis among the genders of the 2 groups did not reveal any significant differences in FMD (p = 0.631 for males and p= 0.767 for females). Similarly, FMD was not age related. More specifically, after dividing patients into two subgroups according to age, using as a cut-off point the age of 60 years, we observed no significant differences (p = 0.453 and p = 0.562 respectively). Importantly, we have shown that T cell population as marked by CD4+ was elevated in UA patients compared to healthy controls (42.07 ± 1.58 vs 35.43 ± 3.1, p = 0.046). Interestingly, a significant difference was detected between the two groups when the T cell subpopulation CD4+CD31null was examined. A significant increase of these circulating cells were found in the UA group (37.33 ± 1.5 vs 28.98 ± 3.1, p = 0.016, Fig. 1B). Similarly, UA patients presented with a significantly elevated frequency of CD4+CD28null T cells (9.49 ± 0.69 vs 6.69 ± 1.19, p = 0.018, Fig. 1C). However, no significant difference between groups was observed in the frequency