Blood Dendritic Cell Levels Associated With Impaired IL-12 Production and T Cell Function in Kidney Disease: Implications for Post-Transplant Viral Infections.

Abstract

Background: We previously demonstrated a reduction of blood myeloid dendritic cell (mDC) levels in patients with kidney disease pre-transplant that is associated statistically with the development of BK viremia and CMV disease post-transplant. However, the mechanisms by which mDC levels might influence these outcomes have not been elucidated. In the current report, we studied the association of mDC levels with mDC IL-12 production and T cell level/function. Methods: Peripheral blood was studied in 3 groups: (i) patients with end stage renal disease at hemodialysis units (HD; n=81); (ii) patients with kidney disease presenting for kidney transplant evaluation or transplantation (Eval/Tx; n=323); and (iii) healthy controls (HC; n=22). Peripheral blood mononuclear cell levels were measured by flow cytometry. IL-12 production was assessed by intracellular staining and multiplex assay. T cell IFN-g responses were measured by ELISpot assay. Results: Along with significant reduction in mDC levels, significantly reduced CD8+ T cell and monocyte levels were also demonstrated in the kidney disease groups compared to HC. Furthermore, levels of CD8+ T cells, which are stimulated by DCs and important to antiviral immunity, correlated positively with the deficient DC levels observed in kidney disease patients. Significantly reduced peripheral blood mDC and monocyte-derived DC (MoDC) IL-12 production was observed after in vitro LPS stimulation in the HD vs HC groups. Finally, addition of autologous MoDCs with or without CMV peptide to T cell culture failed to increase significantly the number of IFN-g responses in the HD group in contrast to that observed for the HC group. Conclusions: Peripheral blood mDC level deficiency in patients with kidney disease is associated with deficient IL-12 production and T cell level/function, which may explain the known correlation of CD8+ T cell lymphopenia with deficient antiviral responses following kidney transplantation.