|
|
Previous Article | Table of Contents | Next Article 
A Monocyte Conditioned Medium Is More Effective Than Defined Cytokines in Mediating the Terminal Maturation of Human Dendritic Cells
Anita Reddy,
Mark Sapp,
Mary Feldman,
Marion Subklewe, and
Nina Bhardwaj
From the Rockefeller University, New York, NY; and the Hospital for Special Surgery, New York, NY.
Mature human dendritic cells can be generated in substantial numbers from nonproliferating progenitors in human blood using a two-step protocol. T cell-depleted mononuclear cells are first cultured with granulocyte-macrophage colony-stimulating factor and interleukin-4 (IL-4) and then exposed to monocyte conditioned medium (MCM). The dendritic cells generated using this approach are rendered terminally mature and are the most potent antigen presenting cells identified to date in humans. We sought to characterize factors in MCM that induce the terminal differentiation of dendritic cells. MCM contained substantial, although varying, quantities of several factors including tumor necrosis factor- , IL-1 , IL-6, and interferon- . However, none of the four factors, individually or in various combinations, could fully substitute for the MCM to generate irreversibly differentiated dendritic cells. The yields, percentage of cells expressing the mature phase marker CD83, and mixed leukocyte reaction-stimulatory function were lower when defined cytokines were used in the place of MCM. Therefore, the full maturation of dendritic cells, because it entails changes in many known cell and molecular properties, requires a number of different cytokines that are released in tandem from appropriately stimulated monocytes. We propose that MCM-matured dendritic cells will be the most effective adjuvants for immunotherapy in vivo.
Blood, Vol. 90 No. 9 (November 1), 1997:
pp. 3640-3646
© 1997 by The American Society of Hematology.

CiteULike Connotea Del.icio.us Digg Reddit Technorati What's this?
This article has been cited by other articles:

|
 |

|
 |
 
D. J. Lee, P. A. Sieling, M. T. Ochoa, S. R. Krutzik, B. Guo, M. Hernandez, T. H. Rea, G. Cheng, M. Colonna, and R. L. Modlin
LILRA2 Activation Inhibits Dendritic Cell Differentiation and Antigen Presentation to T Cells
J. Immunol.,
December 15, 2007;
179(12):
8128 - 8136.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
N. C. Matthews, U. F. Power, and D. J. Reen
Neonatal human autologous dendritic cells pulsed with recombinant protein antigen prime the generation of non-polarized CD4 T-cell effectors
Int. Immunol.,
June 1, 2007;
19(6):
703 - 712.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
F. Perros, P. Dorfmuller, R. Souza, I. Durand-Gasselin, S. Mussot, M. Mazmanian, P. Herve, D. Emilie, G. Simonneau, and M. Humbert
Dendritic cell recruitment in lesions of human and experimental pulmonary hypertension
Eur. Respir. J.,
March 1, 2007;
29(3):
462 - 468.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B. Bleck, D. B. Tse, I. Jaspers, M. A. Curotto de Lafaille, and J. Reibman
Diesel exhaust particle-exposed human bronchial epithelial cells induce dendritic cell maturation.
J. Immunol.,
June 15, 2006;
176(12):
7431 - 7437.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Infantino, B. Moepps, and M. Thelen
Expression and Regulation of the Orphan Receptor RDC1 and Its Putative Ligand in Human Dendritic and B Cells
J. Immunol.,
February 15, 2006;
176(4):
2197 - 2207.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. F. Narvaez, J. Angel, and M. A. Franco
Interaction of Rotavirus with Human Myeloid Dendritic Cells
J. Virol.,
December 1, 2005;
79(23):
14526 - 14535.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. R. Palmer, P. Sun, C. Celluzzi, J. Bisbing, S. Pang, W. Sun, M. A. Marovich, and T. Burgess
Differential Effects of Dengue Virus on Infected and Bystander Dendritic Cells
J. Virol.,
February 15, 2005;
79(4):
2432 - 2439.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. M. Cisco, Z. Abdel-Wahab, J. Dannull, S. Nair, D. S. Tyler, E. Gilboa, J. Vieweg, Y. Daaka, and S. K. Pruitt
Induction of Human Dendritic Cell Maturation Using Transfection with RNA Encoding a Dominant Positive Toll-Like Receptor 4
J. Immunol.,
June 1, 2004;
172(11):
7162 - 7168.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Della Bella, S. Nicola, A. Riva, M. Biasin, M. Clerici, and M. L. Villa
Functional repertoire of dendritic cells generated in granulocyte macrophage-colony stimulating factor and interferon-{alpha}
J. Leukoc. Biol.,
January 1, 2004;
75(1):
106 - 116.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
I. Bedrosian, R. Mick, S. Xu, H. Nisenbaum, M. Faries, P. Zhang, P. A. Cohen, G. Koski, and B. J. Czerniecki
Intranodal Administration of Peptide-Pulsed Mature Dendritic Cell Vaccines Results in Superior CD8+ T-Cell Function in Melanoma Patients
J. Clin. Oncol.,
October 15, 2003;
21(20):
3826 - 3835.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
F. Hladik, A. Desbien, J. Lang, L. Wang, Y. Ding, S. Holte, A. Wilson, Y. Xu, M. Moerbe, S. Schmechel, et al.
Most Highly Exposed Seronegative Men Lack HIV-1-Specific, IFN-{gamma}-Secreting T Cells
J. Immunol.,
September 1, 2003;
171(5):
2671 - 2683.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. Skelton, M. Cooper, M. Murphy, and A. Platt
Human Immature Monocyte-Derived Dendritic Cells Express the G Protein-Coupled Receptor GPR105 (KIAA0001, P2Y14) and Increase Intracellular Calcium in Response to its Agonist, Uridine Diphosphoglucose
J. Immunol.,
August 15, 2003;
171(4):
1941 - 1949.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
F. Moschella, B. Bisikirska, A. Maffei, K. P. Papadopoulos, D. Skerrett, Z. Liu, C. S. Hesdorffer, and P. E. Harris
Gene Expression Profiling and Functional Activity of Human Dendritic Cells Induced with IFN-{alpha}-2b: Implications for Cancer Immunotherapy
Clin. Cancer Res.,
June 1, 2003;
9(6):
2022 - 2031.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Gottschalk, O. L. Edwards, U. Sili, M. H. Huls, T. Goltsova, A. R. Davis, H. E. Heslop, and C. M. Rooney
Generating CTLs against the subdominant Epstein-Barr virus LMP1 antigen for the adoptive immunotherapy of EBV-associated malignancies
Blood,
March 1, 2003;
101(5):
1905 - 1912.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. Messmer, J.-M. Jacque, C. Santisteban, C. Bristow, S.-Y. Han, L. Villamide-Herrera, E. Mehlhop, P. A. Marx, R. M. Steinman, A. Gettie, et al.
Endogenously Expressed nef Uncouples Cytokine and Chemokine Production from Membrane Phenotypic Maturation in Dendritic Cells
J. Immunol.,
October 15, 2002;
169(8):
4172 - 4182.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Lindstedt, B. Johansson-Lindbom, and C. A. K. Borrebaeck
Global reprogramming of dendritic cells in response to a concerted action of inflammatory mediators
Int. Immunol.,
October 1, 2002;
14(10):
1203 - 1213.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Beaulieu, D. F. Robbiani, X. Du, E. Rodrigues, R. Ignatius, Y. Wei, P. Ponath, J. W. Young, M. Pope, R. M. Steinman, et al.
Expression of a Functional Eotaxin (CC Chemokine Ligand 11) Receptor CCR3 by Human Dendritic Cells
J. Immunol.,
September 15, 2002;
169(6):
2925 - 2936.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. Luft, M. Jefford, P. Luetjens, T. Toy, H. Hochrein, K.-A. Masterman, C. Maliszewski, K. Shortman, J. Cebon, and E. Maraskovsky
Functionally distinct dendritic cell (DC) populations induced by physiologic stimuli: prostaglandin E2 regulates the migratory capacity of specific DC subsets
Blood,
July 30, 2002;
100(4):
1362 - 1372.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. M. Timmerman, D. K. Czerwinski, T. A. Davis, F. J. Hsu, C. Benike, Z. M. Hao, B. Taidi, R. Rajapaksa, C. B. Caspar, C. Y. Okada, et al.
Idiotype-pulsed dendritic cell vaccination for B-cell lymphoma: clinical and immune responses in 35 patients
Blood,
March 1, 2002;
99(5):
1517 - 1526.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B. Savoldo, M. L. Cubbage, A. G. Durett, J. Goss, M. H. Huls, Z. Liu, L. Teresita, A. P. Gee, P. D. Ling, M. K. Brenner, et al.
Generation of EBV-Specific CD4+ Cytotoxic T Cells from Virus Naive Individuals
J. Immunol.,
January 15, 2002;
168(2):
909 - 918.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. A. Lyakh, G. K. Koski, H. A. Young, S. E. Spence, P. A. Cohen, and N. R. Rice
Adenovirus type 5 vectors induce dendritic cell differentiation in human CD14+ monocytes cultured under serum-free conditions
Blood,
January 15, 2002;
99(2):
600 - 608.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. Kato, Y. Takaue, and H. Wakasugi
T-cell-conditioned medium efficiently induces the maturation and function of human dendritic cells
J. Leukoc. Biol.,
December 1, 2001;
70(6):
941 - 949.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Somersan, M. Larsson, J. F. Fonteneau, S. Basu, P. Srivastava, and N. Bhardwaj
Primary Tumor Tissue Lysates Are Enriched in Heat Shock Proteins and Induce the Maturation of Human Dendritic Cells
J. Immunol.,
November 1, 2001;
167(9):
4844 - 4852.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B M J Foxwell, S Yoshimura, J Bondeson, F M Brennan, and M Feldmann
High efficiency gene transfer is an efficient way of defining therapeutic targets: a functional genomics approach
Ann Rheum Dis,
November 1, 2001;
60(90003):
iii13 - 17.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. Y. Tsang, M. Zhu, J. Even, J. Gulley, P. Arlen, and J. Schlom
The Infection of Human Dendritic Cells with Recombinant Avipox Vectors Expressing a Costimulatory Molecule Transgene (CD80) to Enhance the Activation of Antigen-specific Cytolytic T Cells
Cancer Res.,
October 1, 2001;
61(20):
7568 - 7576.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Yoshimura, J. Bondeson, B. M. J. Foxwell, F. M. Brennan, and M. Feldmann
Effective antigen presentation by dendritic cells is NF-{{kappa}}B dependent: coordinate regulation of MHC, co-stimulatory molecules and cytokines
Int. Immunol.,
May 1, 2001;
13(5):
675 - 683.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. A. Candido, K. Shimizu, J. C. McLaughlin, R. Kunkel, J. A. Fuller, B. G. Redman, E. K. Thomas, B. J. Nickoloff, and J. J. Mulé
Local Administration of Dendritic Cells Inhibits Established Breast Tumor Growth: Implications for Apoptosis-inducing Agents
Cancer Res.,
January 1, 2001;
61(1):
228 - 236.
[Abstract]
[Full Text]
|
 |
|

|
 |

|
 |
 
R. Ignatius, M. Marovich, E. Mehlhop, L. Villamide, K. Mahnke, W. I. Cox, F. Isdell, S. S. Frankel, J. R. Mascola, R. M. Steinman, et al.
Canarypox Virus-Induced Maturation of Dendritic Cells Is Mediated by Apoptotic Cell Death and Tumor Necrosis Factor Alpha Secretion
J. Virol.,
December 1, 2000;
74(23):
11329 - 11338.
[Abstract]
[Full Text]
|
 |
|

|
 |

|
 |
 
M. V. Dhodapkar, J. W. Young, P. B. Chapman, W. I. Cox, J. F. Fonteneau, S. Amigorena, A. N. Houghton, R. M. Steinman, and N. Bhardwaj
Paucity of Functional T-Cell Memory to Melanoma Antigens in Healthy Donors and Melanoma Patients
Clin. Cancer Res.,
December 1, 2000;
6(12):
4831 - 4838.
[Abstract]
[Full Text]
|
 |
|

|
 |

|
 |
 
K. Schlienger, N. Craighead, K. P. Lee, B. L. Levine, and C. H. June
Efficient priming of protein antigen-specific human CD4+ T cells by monocyte-derived dendritic cells
Blood,
November 15, 2000;
96(10):
3490 - 3498.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. Ignatius, K. Mahnke, M. Rivera, K. Hong, F. Isdell, R. M. Steinman, M. Pope, and L. Stamatatos
Presentation of proteins encapsulated in sterically stabilized liposomes by dendritic cells initiates CD8+ T-cell responses in vivo
Blood,
November 15, 2000;
96(10):
3505 - 3513.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. S. Whittaker, K. S. Bahjat, L. L. Moldawer, and M. J. Clare-Salzler
Autoregulation of Human Monocyte-Derived Dendritic Cell Maturation and IL-12 Production by Cyclooxygenase- 2-Mediated Prostanoid Production
J. Immunol.,
October 15, 2000;
165(8):
4298 - 4304.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. A. Lyakh, G. K. Koski, W. Telford, R. E. Gress, P. A. Cohen, and N. R. Rice
Bacterial Lipopolysaccharide, TNF-{alpha}, and Calcium Ionophore Under Serum-Free Conditions Promote Rapid Dendritic Cell-Like Differentiation in CD14+ Monocytes Through Distinct Pathways That Activate NF-{kappa}B
J. Immunol.,
October 1, 2000;
165(7):
3647 - 3655.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S.-i. Hashimoto, T. Suzuki, S. Nagai, T. Yamashita, N. Toyoda, and K. Matsushima
Identification of genes specifically expressed in human activated and mature dendritic cells through serial analysis of gene expression
Blood,
September 15, 2000;
96(6):
2206 - 2214.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. C. Termeer, J. Hennies, U. Voith, T. Ahrens, J. M. Weiss, P. Prehm, and J. C. Simon
Oligosaccharides of Hyaluronan Are Potent Activators of Dendritic Cells
J. Immunol.,
August 15, 2000;
165(4):
1863 - 1870.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Larsson, D. Messmer, S. Somersan, J.-F. Fonteneau, S. M. Donahoe, M. Lee, P. R. Dunbar, V. Cerundolo, I. Julkunen, D. F. Nixon, et al.
Requirement of Mature Dendritic Cells for Efficient Activation of Influenza A-Specific Memory CD8+ T Cells
J. Immunol.,
August 1, 2000;
165(3):
1182 - 1190.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E. Maraskovsky, E. Daro, E. Roux, M. Teepe, C. R. Maliszewski, J. Hoek, D. Caron, M. E. Lebsack, and H. J. McKenna
In vivo generation of human dendritic cell subsets by Flt3 ligand
Blood,
August 1, 2000;
96(3):
878 - 884.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. TODATE, K. CHIDA, T. SUDA, S. IMOKAWA, J. SATO, K. IDE, T. TSUCHIYA, N. INUI, Y. NAKAMURA, K. ASADA, et al.
Increased Numbers of Dendritic Cells in the Bronchiolar Tissues of Diffuse Panbronchiolitis
Am. J. Respir. Crit. Care Med.,
July 1, 2000;
162(1):
148 - 153.
[Abstract]
[Full Text]
|
 |
|

|
 |

|
 |
 
E. Daro, B. Pulendran, K. Brasel, M. Teepe, D. Pettit, D. H. Lynch, D. Vremec, L. Robb, K. Shortman, H. J. McKenna, et al.
Polyethylene Glycol-Modified GM-CSF Expands CD11bhighCD11chigh But Not CD11blowCD11chigh Murine Dendritic Cells In Vivo: A Comparative Analysis with Flt3 Ligand
J. Immunol.,
July 1, 2000;
165(1):
49 - 58.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Kolb-Maurer, I. Gentschev, H.-W. Fries, F. Fiedler, E.-B. Brocker, E. Kampgen, and W. Goebel
Listeria monocytogenes-Infected Human Dendritic Cells: Uptake and Host Cell Response
Infect. Immun.,
June 1, 2000;
68(6):
3680 - 3688.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
N. Mach, S. Gillessen, S. B. Wilson, C. Sheehan, M. Mihm, and G. Dranoff
Differences in Dendritic Cells Stimulated in Vivo by Tumors Engineered to Secrete Granulocyte-Macrophage Colony-stimulating Factor or Flt3-Ligand
Cancer Res.,
June 1, 2000;
60(12):
3239 - 3246.
[Abstract]
[Full Text]
|
 |
|

|
 |

|
 |
 
G. P. Linette, S. Shankara, S. Longerich, S. Yang, R. Doll, C. Nicolette, F. I. Preffer, B. L. Roberts, and F. G. Haluska
In Vitro Priming with Adenovirus/gp100 Antigen-Transduced Dendritic Cells Reveals the Epitope Specificity of HLA-A*0201-Restricted CD8+ T Cells in Patients with Melanoma
J. Immunol.,
March 15, 2000;
164(6):
3402 - 3412.
[Abstract]
[Full Text]
[PDF]
|
 |
|
|