Prevalence of circulating CD4+CD28null T cells is associated with early atherosclerotic damage in patients with end-stage renal disease undergoing hemodialysis

CD4+ T-cell subsets lacking surface CD28 in peripheral blood have been suggested to predispose people to atherosclerosis. To determine if CD4+CD28null T cells are involved in the immunopathological process of atherosclerotic damage in end-stage renal disease (ESRD) patients undergoing hemodialysis (HD), we characterized peripheral-blood CD4+CD28null T cells from HD patients and investigated the association between these cells and early atherosclerotic damage. Four color flow cytometric analyses showed that HD patients had significantly higher percentages of CD4+CD28null T cells in circulating blood than healthy subjects (HS). Most HD patient-derived CD4+CD28null T cells expressed higher levels of CX3CR1 and produced more intracellular IFN-γ, perforin and granzyme B than their counterparts. Regression analyses demonstrated that the increased levels of CD4+CD28null T cells were positively correlated to serum levels of C-reactive protein, suggesting systemic inflammation and atherosclerosis. Furthermore, phenotypic and functional studies of CD4+CD28null T cells showed that these cells were closely correlated with impaired flow-mediated vasodilation and increased intima-media thickness in the carotid artery, which are markers of early atherosclerosis. These data suggested that CD4+CD28null T cells are important effector cells in HD patients, and that these cells may have a critical role in mediating early atherosclerotic damage.