Renal transplantation reverses functional deficiencies in circulating dendritic cell subsets in chronic renal failure patients.
BACKGROUND
Dendritic cell (DC) subsets play critical roles in regulation of innate and adaptive immune responses. These important antigen-presenting cells have not been extensively analyzed in chronic renal failure (CRF), during dialysis, or before and after renal transplantation.


METHODS
The incidence of circulating precursor (pre)-DC subsets relative to total peripheral blood mononuclear cells was analyzed in healthy controls, haemodialysis patients, peritoneal dialysis patients, CRF patients, and renal transplant (RT) recipients. DC subsets were identified and characterized phenotypically by multicolour flow cytometric analysis and purified by immunomagnetic bead isolation respectively. Cytokine production and circulating DC mobilizing cytokines were determined by ELISA.


RESULTS
The incidence of circulating prePDC was reduced in all patients, but the incidence of circulating preMDC was comparable in RT and dialysis patients compared to healthy controls. CRF patients exhibited the lowest incidence of circulating preMDC and prePDC. Immunomagnetic bead-isolated preMDC and prePDC from haemodialysis patients were functionally impaired (reduced expression of surface costimulatory molecules and interleukin-12p70 production following bacterial lipopolysaccharide stimulation, and reduced interferon-alpha production following herpes simplex virus stimulation respectively, compared to healthy controls and RT recipients. Glomerular filtration rate correlated significantly with the incidence of circulating preMDC, but not prePDC.


CONCLUSIONS
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.
Lim
Wai H
WH
Transplantation Immunology Laboratory and Department of Medicine, The Queen Elizabeth Hospital, Adelaide, South Australia, Australia.
Kireta
Svjetlana
S
Thomson
Angus W
AW
Russ
Graeme R
GR
Coates
P Toby H
PT
D000328:Adult; D000368:Aged; D065095:Calcineurin Inhibitors; D016022:Case-Control Studies; D003713:Dendritic Cells / Q000145:classification / Q000276:immunology*; D005260:Female; D005919:Glomerular Filtration Rate; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007676:Kidney Failure, Chronic / Q000097:blood / Q000276:immunology* / Q000503:physiopathology / Q000601:surgery*; D016030:Kidney Transplantation / Q000276:immunology* / Q000502:physiology; D008297:Male; D008565:Membrane Proteins / Q000097:blood; D008875:Middle Aged; D010531:Peritoneal Dialysis, Continuous Ambulatory; D011446:Prospective Studies; D006435:Renal Dialysis
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D008565:Membrane Proteins; C084881:flt3 ligand protein; D016178:Granulocyte-Macrophage Colony-Stimulating Factor