Progenitor recruitment and in vitro expansion of immunostimulatory dendritic cells from human CD34+ bone marrow cells by c-kit-ligand, GM-CSF and TNFα Conference Paper


Authors: Szabolcs, P.; Feller, E. D.; Moore, M. A. S.; Young, J. W.
Editors: Banchereau, J.; Schmitt, D.
Title: Progenitor recruitment and in vitro expansion of immunostimulatory dendritic cells from human CD34+ bone marrow cells by c-kit-ligand, GM-CSF and TNFα
Conference Title: 3rd International Symposium on Dendritic Cells
Abstract: Several cytokines have been identified that support the development of dendritic cells from murine and human precursor populations, most notably GM-CSF, TNF alpha, and IL-4.(1-7) We have been interested in human bone marrow as a source of defined CD34(+) progenitors to generate large numbers of autologous dendritic cells for use as adjuvants in immune based therapy. In serum-replete conditions with c-kit-ligand, GM-CSF, and TNF alpha, dendritic cells constitute similar to 10-15% of the myeloid progeny (equivalent to similar to 1.7 x 10(6) dendritic cells per single ml of starting bone marrow); and they develop together with granulocytic intermediates and monocytes in the same cultures.(8) CD14(-) dendritic cells share expression of class II MHC and costimulatory ligands with CD14(+) monocyte progeny, but only the CD14(-) HLA-DR(+) dendritic cells are highly stimulatory of resting unprimed T cells.(8) We have further identified a novel colony that develops in the presence of GM-CSF and TNF alpha alongside typical CFU-GM, which is comprised of dendritic cells mixed with less than or equal to 15% monocytes (CFU-DC/mono).(9) c-kit-ligand recruits and expands early progenitors responsive to the dendritic cell-differentiating effects of GM-CSF and TNF alpha, effecting a 100- to 1000-fold greater expansion of CFU-DC/mono by 14d and 21d respectively than does the combination of GM-CSF and TNF alpha without c-kit-ligand.(9) Conclusive proof that dendritic cells have been generated under these in vitro conditions has been founded on the morphologic, phenotypic, and functional criteria that are critical to their identification as potent accessories for primary T cell responses, and their distinction in particular from monocytes.
Keywords: colony-stimulating factor; generation
Journal Title Advances in Experimental Medicine and Biology
Volume: 378
Conference Dates: 1994 Jun 19-24
Conference Location: Annecy, France
ISBN: 0065-2598
Publisher: Springer  
Date Published: 1995-01-01
Start Page: 17
End Page: 20
Language: English
ACCESSION: WOS:A1995BE35J00004
PROVIDER: wos
PUBMED: 8526047
DOI: 10.1007/978-1-4615-1971-3_4
Notes: Proceedings Paper -- Book chapter in "Dendritic Cells in Fundamental and Clinical Immunology. Volume 2" (ISBN: 978-1-4613-5811-4) -- Source: Wos
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  1. James W Young
    301 Young
  2. Malcolm A S Moore
    527 Moore