|
|
 Previous Article | Table of Contents | Next Article 
Blood, Vol. 92 No. 11 (December 1), 1998:
pp. 4238-4247
Generation of Functional Human Dendritic Cells From Adherent
Peripheral Blood Monocytes by CD40 Ligation in the Absence of
Granulocyte-Macrophage Colony-Stimulating Factor
Peter Brossart,
Frank Grünebach,
Gernot Stuhler,
Volker L. Reichardt,
Robert Möhle,
Lothar Kanz, and
Wolfram Brugger
From the University of Tübingen, Department of Hematology,
Oncology and Immunology, Tübingen, Germany.
Recently it has been shown that dendritic cells (DC) can develop
from peripheral blood monocytes when grown in the presence of
granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). However, it is unclear whether DC can also develop from monocytes in absence of these cytokines. We therefore analyzed the effect of Flt-3 ligand (Flt3L) and of CD40 ligand on the
development of human DC from blood monocytes in the absence of GM-CSF.
Adherent peripheral blood mononuclear cells (PBMNC) were cultured in
the presence of different cytokine combinations and analyzed for the
expression of surface molecules and antigen presenting capacity. For
functional analyses, cells were tested for their ability to stimulate
allogeneic T lymphocytes in a mixed lymphocyte reaction (MLR), to
present soluble antigens, and to induce primary HIV-peptide-specific
cytotoxic T-cell (CTL) responses in vitro. Furthermore, expression of
DC-CK1, a recently identified chemokine with specific expression in DC,
and of IL-18 (IGIF), a growth and differentiation factor for Th 1 lymphocytes, was analyzed by reverse-transcription polymerase chain
reaction (RT-PCR). In our study, Flt3L alone was not sufficient to
generate DC and required addition of IL-4. DC generated with Flt3L and
IL-4 underwent maturation after stimulation with tumor necrosis
factor- (TNF-) or CD40L, characterized by CD83 expression,
upregulation of MHC, adhesion, and costimulatory molecules as well as
increased allogeneic proliferative response. In contrast, CD40 ligation
alone promoted differentiation of adherent blood monocytes into
functional DC in the absence of GM-CSF and IL-4. These cells displayed
all phenotypic and functional characteristics of mature DC and were
potent stimulatory cells in priming of major histocompatibility complex
(MHC) class I-restricted CTL responses against an HIV-peptide, whereas
their ability to present soluble protein antigens was reduced. Using a
semiquantitative RT-PCR, DC-CK1 and IL-18 transcripts were detected in
all generated DC populations, independent of growth factors used. Our
findings provide further evidence for the importance of CD40-CD40L
interaction for initiation and maintenance of T-cell responses and
confirm the emerging concept that blood monocytes provide an additional
source of DC depending on external stimuli.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
B. A. Colleton, X.-L. Huang, N. M. Melhem, Z. Fan, L. Borowski, G. Rappocciolo, and C. R. Rinaldo
Primary Human Immunodeficiency Virus Type 1-Specific CD8+ T-Cell Responses Induced by Myeloid Dendritic Cells
J. Virol.,
June 15, 2009;
83(12):
6288 - 6299.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Mariotti, V. Sargentini, C. Marcantonio, E. Todero, R. Teloni, M. C. Gagliardi, A. R. Ciccaglione, and R. Nisini
T-cell-mediated and antigen-dependent differentiation of human monocyte into different dendritic cell subsets: a feedback control of Th1/Th2 responses
FASEB J,
September 1, 2008;
22(9):
3370 - 3379.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Yokoyama, F. Grunebach, S. M. Schmidt, A. Heine, M. Hantschel, S. Stevanovic, H.-G. Rammensee, and P. Brossart
Matrilysin (MMP-7) Is a Novel Broadly Expressed Tumor Antigen Recognized by Antigen-Specific T Cells
Clin. Cancer Res.,
September 1, 2008;
14(17):
5503 - 5511.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. P. Carroll, V. Paunovic, and M. Gadina
Signalling, inflammation and arthritis: Crossed signals: the role of interleukin-15 and -18 in autoimmunity
Rheumatology,
September 1, 2008;
47(9):
1269 - 1277.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. M. Hipp, N. Hilf, S. Walter, D. Werth, K. M. Brauer, M. P. Radsak, T. Weinschenk, H. Singh-Jasuja, and P. Brossart
Sorafenib, but not sunitinib, affects function of dendritic cells and induction of primary immune responses
Blood,
June 15, 2008;
111(12):
5610 - 5620.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. M. Weck, S. Appel, D. Werth, C. Sinzger, A. Bringmann, F. Grunebach, and P. Brossart
hDectin-1 is involved in uptake and cross-presentation of cellular antigens
Blood,
April 15, 2008;
111(8):
4264 - 4272.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Landi, L. A. Babiuk, and S. van Drunen Littel-van den Hurk
High transfection efficiency, gene expression, and viability of monocyte-derived human dendritic cells after nonviral gene transfer
J. Leukoc. Biol.,
October 1, 2007;
82(4):
849 - 860.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. N. Boss, F. Grunebach, K. Brauer, M. Hantschel, V. Mirakaj, T. Weinschenk, S. Stevanovic, H.-G. Rammensee, and P. Brossart
Identification and Characterization of T-Cell Epitopes Deduced from RGS5, a Novel Broadly Expressed Tumor Antigen
Clin. Cancer Res.,
June 1, 2007;
13(11):
3347 - 3355.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. M. Weck, F. Grunebach, D. Werth, C. Sinzger, A. Bringmann, and P. Brossart
TLR ligands differentially affect uptake and presentation of cellular antigens
Blood,
May 1, 2007;
109(9):
3890 - 3894.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Moris, A. Pajot, F. Blanchet, F. Guivel-Benhassine, M. Salcedo, and O. Schwartz
Dendritic cells and HIV-specific CD4+ T cells: HIV antigen presentation, T-cell activation, and viral transfer
Blood,
September 1, 2006;
108(5):
1643 - 1651.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Grunebach, V. Mirakaj, V. Mirakaj, M. R. Muller, T. Brummendorf, and P. Brossart
BCR-ABL Is Not an Immunodominant Antigen in Chronic Myelogenous Leukemia
Cancer Res.,
June 1, 2006;
66(11):
5892 - 5900.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Wierecky, M. R. Muller, S. Wirths, E. Halder-Oehler, D. Dorfel, S. M. Schmidt, M. Hantschel, W. Brugger, S. Schroder, M. S. Horger, et al.
Immunologic and Clinical Responses after Vaccinations with Peptide-Pulsed Dendritic Cells in Metastatic Renal Cancer Patients
Cancer Res.,
June 1, 2006;
66(11):
5910 - 5918.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. d. Nadai, A.-S. Charbonnier, C. Chenivesse, S. Senechal, C. Fournier, J. Gilet, H. Vorng, Y. Chang, P. Gosset, B. Wallaert, et al.
Involvement of CCL18 in Allergic Asthma
J. Immunol.,
May 15, 2006;
176(10):
6286 - 6293.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Nimura, L. F. Zhang, K. Okuma, R. Tanaka, H. Sunakawa, N. Yamamoto, and Y. Tanaka
Cross-linking cell surface chemokine receptors leads to isolation, activation, and differentiation of monocytes into potent dendritic cells.
Experimental Biology and Medicine,
April 1, 2006;
231(4):
431 - 443.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Armeanu, M. Bitzer, I. Smirnow, S. Bossow, S. Appel, G. Ungerechts, C. Bernloehr, W. J. Neubert, U. M. Lauer, and P. Brossart
Severe Impairment of Dendritic Cell Allostimulatory Activity by Sendai Virus Vectors Is Overcome by Matrix Protein Gene Deletion
J. Immunol.,
October 15, 2005;
175(8):
4971 - 4980.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Schutyser, A. Richmond, and J. Van Damme
Involvement of CC chemokine ligand 18 (CCL18) in normal and pathological processes
J. Leukoc. Biol.,
July 1, 2005;
78(1):
14 - 26.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Appel, A. Rupf, M. M. Weck, O. Schoor, T. H. Brummendorf, T. Weinschenk, F. Grunebach, and P. Brossart
Effects of Imatinib on Monocyte-Derived Dendritic Cells Are Mediated by Inhibition of Nuclear Factor-{kappa}B and Akt Signaling Pathways
Clin. Cancer Res.,
March 1, 2005;
11(5):
1928 - 1940.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Moldenhauer, R. C. Frank, J. Pinilla-Ibarz, G. Holland, P. Boccuni, D. A. Scheinberg, A. Salama, K. Seeger, M. A. S. Moore, and S. D. Nimer
Histone deacetylase inhibition improves dendritic cell differentiation of leukemic blasts with AML1-containing fusion proteins
J. Leukoc. Biol.,
September 1, 2004;
76(3):
623 - 633.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. A.B. Joosten, R. L. Smeets, M. I. Koenders, L. A.M. van den Bersselaar, M. M.A. Helsen, B. Oppers-Walgreen, E. Lubberts, Y. Iwakura, F. A.J. van de Loo, and W. B. van den Berg
Interleukin-18 Promotes Joint Inflammation and Induces Interleukin-1-Driven Cartilage Destruction
Am. J. Pathol.,
September 1, 2004;
165(3):
959 - 967.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. C. Roy, G. Bandyopadhyay, S. Rakshit, M. Ray, and S. Bandyopadhyay
IL-4 alone without the involvement of GM-CSF transforms human peripheral blood monocytes to a CD1adim, CD83+ myeloid dendritic cell subset
J. Cell Sci.,
July 15, 2004;
117(16):
3435 - 3445.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Kubo, H. K. Takahashi, M. Takei, H. Iwagaki, T. Yoshino, N. Tanaka, S. Mori, and M. Nishibori
E-Prostanoid (EP)2/EP4 Receptor-Dependent Maturation of Human Monocyte-Derived Dendritic Cells and Induction of Helper T2 Polarization
J. Pharmacol. Exp. Ther.,
June 1, 2004;
309(3):
1213 - 1220.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. R. Muller, G. Tsakou, F. Grunebach, S. M. Schmidt, and P. Brossart
Induction of chronic lymphocytic leukemia (CLL)-specific CD4- and CD8-mediated T-cell responses using RNA-transfected dendritic cells
Blood,
March 1, 2004;
103(5):
1763 - 1769.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. M. Schmidt, K. Schag, M. R. Muller, T. Weinschenk, S. Appel, O. Schoor, M. M. Weck, F. Grunebach, L. Kanz, S. Stevanovic, et al.
Induction of Adipophilin-Specific Cytotoxic T Lymphocytes Using a Novel HLA-A2-Binding Peptide That Mediates Tumor Cell Lysis
Cancer Res.,
February 1, 2004;
64(3):
1164 - 1170.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Appel, A. M. Boehmler, F. Grunebach, M. R. Muller, A. Rupf, M. M. Weck, U. Hartmann, V. L. Reichardt, L. Kanz, T. H. Brummendorf, et al.
Imatinib mesylate affects the development and function of dendritic cells generated from CD34+ peripheral blood progenitor cells
Blood,
January 15, 2004;
103(2):
538 - 544.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. M. Schmidt, K. Schag, M. R. Muller, M. M. Weck, S. Appel, L. Kanz, F. Grunebach, and P. Brossart
Survivin is a shared tumor-associated antigen expressed in a broad variety of malignancies and recognized by specific cytotoxic T cells
Blood,
July 15, 2003;
102(2):
571 - 576.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. R. Muller, F. Grunebach, A. Nencioni, and P. Brossart
Transfection of Dendritic Cells with RNA Induces CD4- and CD8-Mediated T Cell Immunity Against Breast Carcinomas and Reveals the Immunodominance of Presented T Cell Epitopes
J. Immunol.,
June 15, 2003;
170(12):
5892 - 5896.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. K. Takahashi, T. Morichika, H. Iwagaki, T. Yoshino, R. Tamura, S. Saito, S. Mori, T. Akagi, N. Tanaka, and M. Nishibori
Effect of {beta}2-Adrenergic Receptor Stimulation on Interleukin-18-Induced Intercellular Adhesion Molecule-1 Expression and Cytokine Production
J. Pharmacol. Exp. Ther.,
February 1, 2003;
304(2):
634 - 642.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Milazzo, V. L. Reichardt, M. R. Muller, F. Grunebach, and P. Brossart
Induction of myeloma-specific cytotoxic T cells using dendritic cells transfected with tumor-derived RNA
Blood,
February 1, 2003;
101(3):
977 - 982.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Rosenzwajg, F. Jourquin, L. Tailleux, and J. C. Gluckman
CD40 ligation and phagocytosis differently affect the differentiation of monocytes into dendritic cells
J. Leukoc. Biol.,
December 1, 2002;
72(6):
1180 - 1189.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Wysocka, M. H. Zaki, L. E. French, J. Chehimi, M. Shapiro, S. E. Everetts, K. S. McGinnis, L. Montaner, and A. H. Rook
Sezary syndrome patients demonstrate a defect in dendritic cell populations: effects of CD40 ligand and treatment with GM-CSF on dendritic cell numbers and the production of cytokines
Blood,
October 16, 2002;
100(9):
3287 - 3294.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Wirths, J. Reichert, F. Grunebach, and P. Brossart
Activated CD8+ T Lymphocytes Induce Differentiation of Monocytes to Dendritic Cells and Restore the Stimulatory Capacity of Interleukin 10-treated Antigen-presenting Cells
Cancer Res.,
September 1, 2002;
62(17):
5065 - 5068.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Nencioni, F. Grunebach, A. Zobywlaski, C. Denzlinger, W. Brugger, and P. Brossart
Dendritic Cell Immunogenicity Is Regulated by Peroxisome Proliferator-Activated Receptor {gamma}
J. Immunol.,
August 1, 2002;
169(3):
1228 - 1235.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y.-D. Wang, Z.-J. Gu, J.-A. Huang, Y.-B. Zhu, Z.-H. Zhou, W. Xie, Y. Xu, Y.-H. Qiu, and X.-G. Zhang
gp130-linked signal transduction promotes the differentiation and maturation of dendritic cells
Int. Immunol.,
June 1, 2002;
14(6):
599 - 603.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. K. Basak, A. Harui, M. Stolina, S. Sharma, K. Mitani, S. M. Dubinett, and M. D. Roth
Increased dendritic cell number and function following continuous in vivo infusion of granulocyte macrophage-colony-stimulating factor and interleukin-4
Blood,
April 15, 2002;
99(8):
2869 - 2879.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Zheng, A. Chen, R. E. Sterner, P. J. Zhang, T. Pan, N. Kiyatkin, and M. L. Tykocinski
Induction of Antitumor Immunity via Intratumoral Tetra-Costimulator Protein Transfer
Cancer Res.,
November 1, 2001;
61(22):
8127 - 8134.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Brossart, A. Schneider, P. Dill, T. Schammann, F. Grunebach, S. Wirths, L. Kanz, H.-J. Buhring, and W. Brugger
The Epithelial Tumor Antigen MUC1 Is Expressed in Hematological Malignancies and Is Recognized by MUC1-specific Cytotoxic T-Lymphocytes
Cancer Res.,
September 1, 2001;
61(18):
6846 - 6850.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Novak, T. Bieber, and N. Katoh
Engagement of Fc{{epsilon}}RI on Human Monocytes Induces the Production of IL-10 and Prevents Their Differentiation in Dendritic Cells
J. Immunol.,
July 15, 2001;
167(2):
797 - 804.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Vankayalapati, B. Wizel, D. L. Lakey, Y. Zhang, K. A. Coffee, D. E. Griffith, and P. F. Barnes
T Cells Enhance Production of IL-18 by Monocytes in Response to an Intracellular Pathogen
J. Immunol.,
June 1, 2001;
166(11):
6749 - 6753.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Caron, Y. Delneste, E. Roelandts, C. Duez, N. Herbault, G. Magistrelli, J.-Y. Bonnefoy, J. Pestel, and P. Jeannin
Histamine Induces CD86 Expression and Chemokine Production by Human Immature Dendritic Cells
J. Immunol.,
May 15, 2001;
166(10):
6000 - 6006.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Seiffert, P. Brossart, C. Cant, M. Cella, M. Colonna, W. Brugger, L. Kanz, A. Ullrich, and H.-J. Buhring
Signal-regulatory protein {alpha} (SIRP{alpha}) but not SIRP{beta} is involved in T-cell activation, binds to CD47 with high affinity, and is expressed on immature CD34+CD38{-} hematopoietic cells
Blood,
May 1, 2001;
97(9):
2741 - 2749.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Yu, M. Hagihara, K. Ando, B. Gansuvd, H. Matsuzawa, T. Tsuchiya, Y. Ueda, H. Inoue, T. Hotta, and S. Kato
Enhancement of Human Cord Blood CD34+ Cell-Derived NK Cell Cytotoxicity by Dendritic Cells
J. Immunol.,
February 1, 2001;
166(3):
1590 - 1600.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Brossart, S. Wirths, G. Stuhler, V. L. Reichardt, L. Kanz, and W. Brugger
Induction of cytotoxic T-lymphocyte responses in vivo after vaccinations with peptide-pulsed dendritic cells
Blood,
November 1, 2000;
96(9):
3102 - 3108.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. S. Kornbluth
The emerging role of CD40 ligand in HIV infection
J. Leukoc. Biol.,
September 1, 2000;
68(3):
373 - 382.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Klein, H. Bueler, and R. C. Mulligan
Comparative Analysis of Genetically Modified Dendritic Cells and Tumor Cells as Therapeutic Cancer Vaccines
J. Exp. Med.,
May 15, 2000;
191(10):
1699 - 1708.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. D. Roth, B. J. Gitlitz, S. M. Kiertscher, A. N. Park, M. Mendenhall, N. Moldawer, and R. A. Figlin
Granulocyte Macrophage Colony-stimulating Factor and Interleukin 4 Enhance the Number and Antigen-presenting Activity of Circulating CD14+ and CD83+ Cells in Cancer Patients
Cancer Res.,
April 1, 2000;
60(7):
1934 - 1941.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
S. Riegler, H. Hebart, H. Einsele, P. Brossart, G. Jahn, and C. Sinzger
Monocyte-derived dendritic cells are permissive to the complete replicative cycle of human cytomegalovirus
J. Gen. Virol.,
February 1, 2000;
81(2):
393 - 399.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
K. Crawford, D. Gabuzda, V. Pantazopoulos, J. Xu, C. Clement, E. Reinherz, and C. A. Alper
Circulating CD2+ Monocytes Are Dendritic Cells
J. Immunol.,
December 1, 1999;
163(11):
5920 - 5928.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Seiffert, C. Cant, Z. Chen, I. Rappold, W. Brugger, L. Kanz, E. J. Brown, A. Ullrich, and H.-J. Buhring
Human Signal-Regulatory Protein Is Expressed on Normal, But Not on Subsets of Leukemic Myeloid Cells and Mediates Cellular Adhesion Involving Its Counterreceptor CD47
Blood,
December 1, 1999;
94(11):
3633 - 3643.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
