Growth Factor-Induced Mobilization of Dendritic Cells in Kidney and Liver of Rhesus Macaques: Implications for Transplantation

Abstract

Hematopoietic growth factors (HGF) mobilize potential tolerogenic cells in transplant donors. Fms-like tyrosine kinase 3 ligand (Flt3L) mobilizes stem cells and dendritic cells (DCs) in human and nonhuman primate blood. Blood and renal and liver biopsies were obtained from untreated and Flt3L-mobilized rhesus macaques. Flt3L increased the number of myeloid CD11c(hi) and plasmacytoid CD123(hi) precursors in blood and both myeloid CD11c(+) HLA-DR(+) fascin(+) (CD45RA(-)) DCs and putative plasmacytoid CD11c(lo) CD45RA(hi) DC precursors in liver and kidneys, without affecting organ function. DC in Flt3L-treated monkeys were concentrated in the glomeruli and interstitium of kidneys, and in the portal triads and parenchyma of liver. These DCs exhibited the phenotype of immature antigen-presenting cells (APCs; CD83(-) CD86(lo) CCR5(+) CCR7(-)). HGF-induced changes reversed significantly within 7 days of Flt3L withdrawal. Therapeutic protocols that mobilize donor hematopoietic cells should consider the influence of HGF on the APC constituency of prospective organ allografts.