Renal Transplantation Reverses Functional Deficiencies in Circulating Dendritic Cell Subsets in Chronic Renal Failure Patients

Abstract

Deficiencies in the incidence and function of precursor DC can be reversed with successful renal transplantation achieving normal renal function. However, the finding of reduced incidence of circulating prePDC in the peripheral blood in RT recipients may be of significance in the pathogenesis of infections and malignancies.

Differentiation of Monocyte Derived Dendritic Cells in End Stage Renal Disease is Skewed Towards Accelerated Maturation

“…This hypothesis was recently supported in patients undergoing renal transplantation, where the afore existing deficiencies in incidence and function of precursor DC were reversed [27]. Moreover, serum from uremic patients, when added to culture medium, impaired DC-function in vitro, especially endocytosis and maturation [28].…”

Human plasmacytoid dendritic cells regulate immune responses to Epstein-Barr virus (EBV) infection and delay EBV-related mortality in humanized NOD-SCID mice

“…We and others have previously shown that circulating precursor PDCs are reduced in renal and cardiac transplant recipients. 18,22,23 PDCs isolated from recipients of renal transplants were functionally normal in response to viral stimulation, suggesting that the defect in antiviral response in renal transplant recipients was a reflection of the reduction in circulating precursor PDCs rather than an intrinsic abnormality of PDCs. Thus, the present studies were performed to address the consequence of reduced PDCs in the pathogenesis of EBV-related diseases using a NOD-SCID mouse lymphoma model.…”

“…Flow cytometric analysis of PDC-depleted PBMC fraction stained with anti-human CD123 ϩ mAbs confirmed approximately 50% reduction in the proportion of PDCs of total PBMCs approximately corresponding to the reduced proportion of PDCs in the peripheral blood of renal transplant recipients. 18 PDC-enriched PBMC mice received a further 1 ϫ 10 5 autologous PDCs from the same blood donor (positively isolated using Automacs) injected into each mouse in addition to PBMCs. The depletion and enrichment of PDCs were performed using BDCA-4 ϩ isolation kit and cells separated by Automacs as described.…”

“…The depletion and enrichment of PDCs were performed using BDCA-4 ϩ isolation kit and cells separated by Automacs as described. 18 In the IFN-␣-pulsed PBMC group, PBMCs were cultured overnight at a concentration of 1 ϫ 10 8 in 10 mL complete medium supplemented with IFN-␣ (1000 U/mL). Because all mice were reconstituted with PBMCs from the same blood donors, observed differences were not attributed to interindividual donor risk of EBV infection.…”

“…17 In a previous study, we demonstrated that circulating pre-PDCs are severely reduced in the peripheral blood of renal transplant recipients resulting in impaired IFN-␣ production by PBMCs following viral stimulation. 18 We hypothesized that the reduction in circulating pre-PDCs observed in transplant recipients plays a crucial role in the risk of viral infection, and in particular EBV-related infection and the onset of LPD. In the present study, we address this hypothesis by assessing the impact of a reduction in the numbers of circulating PDCs in the development of EBVrelated infection and LPD using a humanized NOD-SCID mouse model as a surrogate model of human EBV infection.…”