CD34+ hematopoietic progenitors from human cord blood differentiate along two independent dendritic cell pathways in response to GM-CSF+TNF alpha.

Abstract

SummaryHuman dendritic cells (DC) can now be generated in vitro in large numbers by culturing CD34 + hematopoietic progenitors in presence of GM-CSF+TNFet for 12 d. The present study demonstrates that cord blood CD34 + HPC indeed differentiate along two independent DC pathways. At early time points (day 5-7) during the culture, two subsets of DC precursors identified by the exclusive expression of CDla and CD14 emerge independently. Both precursor subsets mature at day 12-14 into DC with typical morphology and phenotype (CDS0, CD83, CD86, CD58, high HLA class II). CDla + precursors give rise to cells characterized by the expression of Birbeck granules, the Lag antigen and E-cadherin, three markers specifically expressed on Langerhans cells in the epidermis. In contrast, the CD14 + progenitors mature into CDla + DC lacking Birbeck granules, E-cadherin, and Lag antigen but expressing CD2, CD9, CD68, and the coagulation factor XIlla described in dermal dendritic cells. The two mature DC were equally potent in stimulating allogeneic CD45RA + naive T cells. Interestingly, the CD14 + precursors, but not the CDla + precursors, represent bipotent cells that can be induced to differentiate, in response to M-CSF, into macrophage-like cells, lacking accessory function for T ceils.Altogether, these results demonstrate that different pathways of DC development exist: the Langerhans cells and the CD14+-derived DC related to dermal DC or circulating blood DC. The physiological relevance of these two pathways of DC development is discussed with regard to their potential in vivo counterparts.

Tumor‐associated macrophages correlate with response to epidermal growth factor receptor‐tyrosine kinase inhibitors in advanced non‐small cell lung cancer

“…First, although CD68 is widely used to identify macrophages, 22,28 it is also expressed on other cell types, such as immature CD1a-positive dendritic cells. 32,33 Gottfried et al also reported that CD68 could be expressed on fibroblasts. 34 Counterstaining with cell type-specific markers in our study did reveal that very low ratio of CD68þ cells were fibroblasts or dendritic cells (Supporting Information Figures 2A and 2B).…”

Generation of dendritic cell-based vaccines for cancer therapy

“…DC can either be generated from proliferating CD34 + bone marrow precursor cells (Caux et al, 1996) -which differentiate under a variety of different cytokines including SCF, Flt3, GM -CSF, TGF-b and TNF-a -or from non-proliferating peripheral CD14 + cells (monocytes) (Sallusto and Lanzavecchia, 1994). Usually, CD34 + precursors mobilised by G-CSF are isolated by leukapheresis to obtain high numbers of peripheral cells for therapeutical purposes.…”

Regulation of Mucosal Dendritic Cell Function by Receptor Activator of NF-κB (RANK)/RANK Ligand Interactions: Impact on Tolerance Induction

“…An integral role for several TNF/ TNFR family members in DC biology has recently emerged. TNF and CD40 ligand (CD40L) are both involved in the differentiation of DC from CD34 ϩ progenitor cells (13), and CD40L plays a role in DC survival and can elicit DC cytokine production (14). More recently, a new member of the TNFR family, receptor activator of NF-B (RANK), and its ligand (RANKL; also known as TNFrelated activation-induced cytokine, osteoclast differentiation factor, and osteoprotegrin ligand) have been cloned (15,16).…”