Functional impairment of monocyte-derived dendritic cells in patients with severe chronic kidney disease

Abstract

Background. Dendritic cells (DCs) are antigen-presenting cells that are pivotal for the initiation of the primary immune response. Patients with chronic kidney disease (CKD) with or without chronic intermittent haemodialysis (CIHD) show an impaired immune response. Dysfunction of DCs may underlie this phenomenon. Methods. In this study, several different functions of monocyte-derived DCs (moDC) of patients with CKD class IV-V (glomerular filtration rate <30 ml/min) and patients on CIHD were studied in vitro and compared with age- and sex-matched healthy volunteers. Results. We demonstrate that, independent of the maturation stimulus used, mature moDC from both groups of patients did not acquire the same level of terminal differentiation as moDC from controls, as shown by analysis of cell surface markers and the relative high macropinocytosis activity of moDC. The stimulation of allogeneic T-cells by immature moDC and mature moDC did not differ between patients and controls. However, in the presence of immature moDC or antigen-loaded maturated moDC from patients, less proliferation of autologous T-cells was observed in response to recall antigens. There was no difference between moDC from controls and patients in their ability to activate naive T-cells and to differentiate them into Th1 and Th2 cells. Conclusions. These results show that the terminal differentiation of moDC in patients with severe CKD is impaired. This impairment is not restricted to one maturation stimulus and is independent of treatment with haemodialysis. © 2007 Oxford University Press.