PMID- 10687137
OWN - NLM
STAT- MEDLINE
DCOM- 20000511
LR  - 20191103
IS  - 1524-9557 (Print)
IS  - 1524-9557 (Linking)
VI  - 23
IP  - 1
DP  - 2000 Jan
TI  - Dendritic cells generated from CD34+ progenitor cells with flt3 ligand, c-kit 
      ligand, GM-CSF, IL-4, and TNF-alpha are functional antigen-presenting cells 
      resembling mature monocyte-derived dendritic cells.
PG  - 48-58
AB  - Dendritic cells (DCs) are powerful antigen-presenting cells. Because DCs are rare 
      cells, methods to produce them in vitro are valuable ways to study their biologic 
      properties and to generate cells for immunotherapy. This study defines the 
      antigen-presenting properties of DCs generated in vitro from CD34+ cells of 
      patients with breast cancer. The combination of cytokines flt3 ligand + c-kit 
      ligand + granulocyte-macrophage colony-stimulating factor (GM-CSF) + 
      interleukin-4 (IL-4) + tumor necrosis factor-alpha (TNF-alpha) was used to 
      maximize the output of mature DCs in the culture of CD34+ cells while minimizing 
      the production of monocytes. Cells grew and differentiated into DCs as measured 
      by a time-dependent upregulation of cell surface antigens major 
      histocompatibility complex class II, CD1a, CD80, CD86, CD40, and CD4, so that 40% 
      +/- 9% (n = 6) of cells in culture at day 15 were CD1a+CD14-. Markers were 
      acquired in the same sequence as on monocytes induced to differentiate with 
      GM-CSF + IL-4. Differentiation was marked by a time-dependent increase in 
      allostimulatory function, which, at its peak, was more potent than in cultures of 
      DCs generated from monocytes with GM-CSF + IL-4, but was comparable on a 
      cell-to-cell basis to that of mature monocytes cultured in flt3-ligand + 
      c-kit-ligand + GM-CSF + IL-4 + TNF-alpha. Both CD34+ cell-derived and 
      monocyte-derived DCs were able to process and to present tetanus toxoid and 
      keyhole limpet hemocyanin to autologous T cells and to present major 
      histocompatibility class I-binding peptides to CD8+ cytotoxic T lymphocytes 
      inducing interferon-gamma production. Altogether, these results suggest that DCs 
      generated from CD34+ cells of patients with breast cancer with flt3 ligand, c-kit 
      ligand, GM-CSF, IL-4, and TNF-alpha are competent antigen-presenting cells, 
      particularly for CD8+ cytotoxic T lymphocytes, and resemble mature 
      monocyte-derived DCs in the assays described here.
FAU - Ferlazzo, G
AU  - Ferlazzo G
AD  - Karmanos Cancer Institute, Wayne State University, Detroit, Michigan 48201, USA.
FAU - Klein, J
AU  - Klein J
FAU - Paliard, X
AU  - Paliard X
FAU - Wei, W Z
AU  - Wei WZ
FAU - Galy, A
AU  - Galy A
LA  - eng
GR  - 1R01CA 76340-01/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Immunother
JT  - Journal of immunotherapy (Hagerstown, Md. : 1997)
JID - 9706083
RN  - 0 (Antigens, CD34)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Isoantigens)
RN  - 0 (Membrane Proteins)
RN  - 0 (Stem Cell Factor)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (flt3 ligand protein)
RN  - 207137-56-2 (Interleukin-4)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
SB  - IM
MH  - Adult
MH  - Antigen Presentation/immunology
MH  - Antigen-Presenting Cells/cytology/drug effects/immunology/ultrastructure
MH  - *Antigens, CD34/immunology
MH  - Biomarkers, Tumor
MH  - Breast Neoplasms/immunology
MH  - Cell Differentiation/drug effects
MH  - Dendritic Cells/cytology/drug effects/*immunology/ultrastructure
MH  - Female
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/immunology/*pharmacology
MH  - Hematopoietic Stem Cells/cytology/*drug effects/immunology/ultrastructure
MH  - Histocompatibility Antigens Class I/immunology
MH  - Humans
MH  - Immunophenotyping
MH  - Interleukin-4/immunology/*pharmacology
MH  - Isoantigens/immunology
MH  - Membrane Proteins/immunology/*pharmacology
MH  - Monocytes/*immunology
MH  - Solubility
MH  - Stem Cell Factor/immunology/*pharmacology
MH  - Tumor Cells, Cultured
MH  - Tumor Necrosis Factor-alpha/immunology/*pharmacology
EDAT- 2000/02/25 09:00
MHDA- 2000/05/16 09:00
CRDT- 2000/02/25 09:00
PHST- 2000/02/25 09:00 [pubmed]
PHST- 2000/05/16 09:00 [medline]
PHST- 2000/02/25 09:00 [entrez]
AID - 10.1097/00002371-200001000-00007 [doi]
PST - ppublish
SO  - J Immunother. 2000 Jan;23(1):48-58. doi: 10.1097/00002371-200001000-00007.