Expansion of immunostimulatory dendritic cells among the myeloid progeny of human CD34(+) bone marrow precursors cultured with c-kit ligand, granulocytemacrophage colony-stimulating factor, and TNF-α(1,2) Journal Article


Authors: Szabolcs, P.; Moore, M. A. S.; Young, J. W.
Article Title: Expansion of immunostimulatory dendritic cells among the myeloid progeny of human CD34(+) bone marrow precursors cultured with c-kit ligand, granulocytemacrophage colony-stimulating factor, and TNF-α(1,2)
Abstract: Human CD34+ bone marrow progenitors cultured in the presence of granulocyte-macrophage CSF (CM-CSF) develop along a myeloid pathway, and the addition of exogenous TNF-α leads to the differentiation of dendritic cells among the myeloid progeny. These bone marrow CD34+-derived dendritic cells that develop during 2-wk culture have the same morphologic, phenotypic, and functional properties that distinguish mature dendritic cells in blood, c-kit ligand does not directly influence dendritic cell differentiation per se, but rather increases the total cell number in synergistic combination with GM-CSF and TNF-α. This degree of expansion translates into an effective yield of ∼ 1.7 × 106 mature dendritic cells per single ml of normal adult human bone marrow, compared with ∼106 dendritic cells usually obtained from 450 to 500 ml of peripheral blood. In addition to dendritic cells that constitute ∼10 to 15% of the total myeloid progeny, the cultures contain monocytes/macrophages and intermediate granulocytic precursors. Monocytes/macrophages and dendritic cells together comprise all of the class II MHC-positive progeny. Sorted cells bearing the CD14+ HLA-DR+ phenotype of mature monocytes are at least 1.5 to 2 logs less active than CD14- HLA-DR+ dendritic cells as stimulators in the allogeneic MLR, even though both CD14+ and CD14- subpopulations share expression of several costimulatory ligands. The synergistic combination of c-kit ligand, GM-CSF, and TNF-α therefore expands substantial numbers of immunostimulatory CD14- HLA-DR+ dendritic cells from defined CD34+ progenitors in human bone marrow. This should facilitate the use of dendritic cells in the manipulation of T cell-mediated immune responses. Copyright © 1995 by The American Association of Immunologists.
Keywords: controlled study; human cell; proto-oncogene proteins; drug potentiation; flow cytometry; lymphocyte proliferation; antigens, cd3; bone marrow cells; cells, cultured; cell division; cd34 antigen; gene expression; dendritic cell; cell differentiation; monoclonal antibody; antigen presentation; dendritic cells; lymphocyte culture test, mixed; cellular immunity; immunotherapy; hla dr antigen; major histocompatibility antigen class 2; immunostimulation; hematopoietic stem cell; receptor protein-tyrosine kinases; antigens, cd; monocyte; macrophage; okt 4; antigens, cd34; recombinant erythropoietin; t lymphocyte subpopulation; recombinant granulocyte macrophage colony stimulating factor; cd14 antigen; mixed lymphocyte reaction; tumor necrosis factor; soybean agglutinin; recombinant interleukin 3; granulocyte-macrophage colony-stimulating factor; okt 3; human; priority journal; article; recombinant tumor necrosis factor alpha; steel factor; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; recombinant interleukin 6; proto-oncogene protein c-kit; receptors, colony-stimulating factor; 4 (2 hydroxyethyl) 1 piperazineethanesulfonic acid; okt 6; phycoerythrin; bone marrow culture
Journal Title: Journal of Immunology
Volume: 154
Issue: 11
ISSN: 0022-1767
Publisher: The American Association of Immunologists, Inc  
Date Published: 1995-06-01
Start Page: 5851
End Page: 5861
Language: English
PUBMED: 7538534
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 28 August 2018 -- Source: Scopus
Citation Impact
MSK Authors
  1. James W Young
    301 Young
  2. Malcolm A S Moore
    527 Moore