Identification of dendritic cell colony-forming units among normal human CD34+ bone marrow progenitors that are expanded by c-kit-ligand and yield pure dendritic cell colonies in the presence of granulocyte/macrophage colony-stimulating factor and tumor necrosis factor α Journal Article


Authors: Young, J. W.; Szabolcs, P.; Moore, M. A. S.
Article Title: Identification of dendritic cell colony-forming units among normal human CD34+ bone marrow progenitors that are expanded by c-kit-ligand and yield pure dendritic cell colonies in the presence of granulocyte/macrophage colony-stimulating factor and tumor necrosis factor α
Abstract: Several cytokines, especially granulocyte/macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor α (TNF-α, have been identified that foster the development of dendritic cells from blood and bone marrow precursors in suspension cultures. These precursors are reported to be infrequent or to yield small numbers of dendritic cells in colony-forming assays. Here we readily identify dendritic cell colony-forming units (CFU-DC) that give rise to pure dendritic cell colonies. Human CD34+ bone marrow progenitors were expanded in semisolid cultures with serum-replete medium containing c-kit-hgand, GM-CSF, and TNF-α. The addition of TNF-α to GM-CSF did not alter the number of typical GM colonies but did generate pure dendritic cell colonies that accounted for N40% of the total colony growth. When the two distinct types of colonies were plucked from methylcellulose and tested for T cellstimulatory activity in the mixed leukocyte reaction, the potency of colony-derived dendritic cells exceeded that of CFU-GM progeny from the same cultures by at least 1.5-2 logs. Immunophenotyping and cytochemical staining of the CFU-DC-derived progeny was also characteristic of dendritic cells. Other myeloid cells were not identified in these colonies. The addition of c-kit-ligand to GM-CSF- and TNF-α-supplemented suspensions of CD34+ bone marrow cells expanded CFU-DCs almost 100-fold by 14 d. We conclude that normal human CD34+ bone marrow cells include substantial numbers ofclonogenic progenitors, distinct from CFU-GMs, that can give rise to pure dendritic cell colonies. These CFU-DCs can be expanded for several weeks by in vitro culture with c-kit-ligand, and their differentiation requires exogenous TNF-α in addition to GM-CSF. We speculate that this dendritic cell-committed pathway may in the steady state contribute cells to the epidermis and afferent lymph, where dendritic cells are the principal myeloid cell type, and may increase the numbers of these specialized antigen-presenting cells during T cell-mediated immune responses. © 1995, Rockefeller University Press., All rights reserved.
Keywords: human cell; bone marrow cells; cd34 antigen; stem cell factor; bone marrow; dendritic cell; granulocyte macrophage colony stimulating factor; cell differentiation; dose-response relationship, drug; stem cell; dendritic cells; cellular immunity; tumor necrosis factor alpha; hematopoietic stem cells; immunophenotyping; hematopoiesis; bone marrow cell; colony-forming units assay; antigens, cd34; histocytochemistry; clone cells; drug interactions; antigen presenting cell; tumor necrosis factor; colony forming unit; growth substances; colony formation; granulocyte-macrophage colony-stimulating factor; human; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.
Journal Title: Journal of Experimental Medicine
Volume: 182
Issue: 4
ISSN: 0022-1007
Publisher: Rockefeller University Press  
Date Published: 1995-10-01
Start Page: 1111
End Page: 1119
Language: English
DOI: 10.1084/jem.182.4.1111
PUBMED: 7561684
PROVIDER: scopus
PMCID: PMC2192302
DOI/URL:
Notes: Article -- Export Date: 28 August 2018 -- Source: Scopus
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MSK Authors
  1. James W Young
    300 Young
  2. Malcolm A S Moore
    526 Moore