Characterization of CD4+CD28null T cells in patients with coronary artery disease and individuals with risk factors for atherosclerosis

Risk factors for atherosclerosis may contribute to chronic low-grade inflammation. A highly cytotoxic and inflammatory CD4+ cell subset (CD4+CD28null cells) has been associated with inflammatory diseases, including acute coronary syndromes (ACS). The aim of this study was to quantify and characterize CD4+CD28null cells in individuals with risk factors for atherosclerosis and patients with coronary artery disease (CAD). In order to achieve this goal, peripheral blood mononuclear cells (PBMCs) from individuals with risk factors for atherosclerosis and patients with CAD were analyzed using flow cytometry to detect cytotoxic molecules and evaluate the expression of homing receptors and inflammatory cytokines in CD4+ cell subsets. The cells were evaluated ex vivo and after stimulation in culture. We found no differences in the proportions of CD4+CD28null cells among the groups. Compared with the CD4+CD28+ population, the ex vivo CD4+CD28null subset from all groups expressed higher levels of granzymes A and B, perforin, granulysin and interferon-γ (IFN-γ). Individuals with risk factors and patients with ACS showed the highest levels of cytotoxic molecules. After stimulation, tumor necrosis factor-α (TNF-α) expression in the CD4+CD28null subset from these groups increased more than in the other groups. Stimulation with LPS decreased the expression of cytotoxic molecules by CD4+CD28null cells in all groups. In conclusion, our results show that risk factors for atherosclerosis may alter the CD4+CD28null cells phenotype, increasing their cytotoxic potential. Our findings also suggest that CD4+CD28null cells may participate in the early phases of atherosclerosis.

► Risk factors for atherosclerosis may lead to chronic low-grade inflammatory processes.
► Cytotoxic and inflammatory CD4+CD28null cells are associated with inflammation.
► We evaluated CD4+CD28null cells regarding its cytotoxic and inflammatory potentials.
► Risk factors for atherosclerosis increased CD4+CD28null cells pathogenic features.
► The results support the anti-inflammatory treatment for patients with risk factors.