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Blood, 15 December 2001, Vol. 98, No. 13, pp. 3520-3526
PLENARY PAPER
Isolation and characterization of plasmacytoid dendritic cells
from Flt3 ligand and granulocyte-macrophage colony-stimulating
factor-treated mice
Pia Björck
From the Department of Dermatology, University of
Pittsburgh, PA.
Interferon / plays an important role in the first-line
defense against viral infections and can modulate cytokine responses by
T-helper cells. Type 1 interferons (IFNs) are clinically important in
infectious diseases and in the treatment of leukemia and lymphomas. Many different cell types have the capacity to produce IFN- after encounter with virus and bacteria. The major, natural type 1 IFN-producing cell in humans was recently described as the
plasmacytoid T cell, or pDC2, and it can differentiate into dendritic
cells (DCs) on culture. This study describes the murine natural
IFN- -producing cell, or pDC2, that shares morphologic features with
its human counterpart but has some distinct phenotypical
characteristics. Murine plasmacytoid DCs can be differentially isolated
based on their expression of CD11c, B220 (CD45R), and Thy1.2 (CD90).
They lack expression of myeloid (eg, CD11b) antigens and CD8 , a
marker used to isolate lymphoid DCs. Like human pDC2, murine
plasmacytoid DCs exhibit their maximal type 1 IFN-producing capacity
at a precursor stage; pDCs isolated from bone marrow responded to viral
stimulation with higher IFN- production than cells of the same
phenotype isolated from spleen. Mobilization of mice with Flt3 ligand
(Flt3L) or Flt3L and granulocyte-macrophage colony-stimulating factor, hematopoietic factors that specifically enhance DC growth, resulted in
strikingly increased numbers of pDC in bone marrow and spleen. The
isolation of this novel murine DC subset may serve as a useful tool in
the study of viral immunobiology and for the design of treatments for
murine malignancies.

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October 1, 2003;
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6478 - 6487.
[Abstract]
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A. D'Amico and L. Wu
The Early Progenitors of Mouse Dendritic Cells and Plasmacytoid Predendritic Cells Are within the Bone Marrow Hemopoietic Precursors Expressing Flt3
J. Exp. Med.,
July 21, 2003;
198(2):
293 - 303.
[Abstract]
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H. Karsunky, M. Merad, A. Cozzio, I. L. Weissman, and M. G. Manz
Flt3 Ligand Regulates Dendritic Cell Development from Flt3+ Lymphoid and Myeloid-committed Progenitors to Flt3+ Dendritic Cells In Vivo
J. Exp. Med.,
July 21, 2003;
198(2):
305 - 313.
[Abstract]
[Full Text]
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A. D. Edwards, D. Chaussabel, S. Tomlinson, O. Schulz, A. Sher, and C. Reis e Sousa
Relationships Among Murine CD11chigh Dendritic Cell Subsets as Revealed by Baseline Gene Expression Patterns
J. Immunol.,
July 1, 2003;
171(1):
47 - 60.
[Abstract]
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E. Muraille, C. De Trez, B. Pajak, F. A. Torrentera, P. De Baetselier, O. Leo, and Y. Carlier
Amastigote Load and Cell Surface Phenotype of Infected Cells from Lesions and Lymph Nodes of Susceptible and Resistant Mice Infected with Leishmania major
Infect. Immun.,
May 1, 2003;
71(5):
2704 - 2715.
[Abstract]
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C. M. Smith, G. T. Belz, N. S. Wilson, J. A. Villadangos, K. Shortman, F. R. Carbone, and W. R. Heath
Cutting Edge: Conventional CD8{alpha}+ Dendritic Cells Are Preferentially Involved in CTL Priming After Footpad Infection with Herpes Simplex Virus-1
J. Immunol.,
May 1, 2003;
170(9):
4437 - 4440.
[Abstract]
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J.-F. Fonteneau, M. Gilliet, M. Larsson, I. Dasilva, C. Munz, Y.-J. Liu, and N. Bhardwaj
Activation of influenza virus-specific CD4+ and CD8+ T cells: a new role for plasmacytoid dendritic cells in adaptive immunity
Blood,
May 1, 2003;
101(9):
3520 - 3526.
[Abstract]
[Full Text]
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A. Krug, R. Veeraswamy, A. Pekosz, O. Kanagawa, E. R. Unanue, M. Colonna, and M. Cella
Interferon-producing Cells Fail to Induce Proliferation of Naive T Cells but Can Promote Expansion and T Helper 1 Differentiation of Antigen-experienced Unpolarized T Cells
J. Exp. Med.,
April 7, 2003;
197(7):
899 - 906.
[Abstract]
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M. Dalod, T. Hamilton, R. Salomon, T. P. Salazar-Mather, S. C. Henry, J. D. Hamilton, and C. A. Biron
Dendritic Cell Responses to Early Murine Cytomegalovirus Infection: Subset Functional Specialization and Differential Regulation by Interferon {alpha}/{beta}
J. Exp. Med.,
April 7, 2003;
197(7):
885 - 898.
[Abstract]
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A. M. Woltman and C. van Kooten
Functional modulation of dendritic cells to suppress adaptive immune responses
J. Leukoc. Biol.,
April 1, 2003;
73(4):
428 - 441.
[Abstract]
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V. Pullarkat, P. P. Lee, R. Scotland, V. Rubio, S. Groshen, C. Gee, R. Lau, J. Snively, S. Sian, S. L. Woulfe, et al.
A Phase I Trial of SD-9427 (Progenipoietin) with a Multipeptide Vaccine for Resected Metastatic Melanoma
Clin. Cancer Res.,
April 1, 2003;
9(4):
1301 - 1312.
[Abstract]
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S. Vollstedt, M. Franchini, H. P. Hefti, B. Odermatt, M. O'Keeffe, G. Alber, B. Glanzmann, M. Riesen, M. Ackermann, and M. Suter
Flt3 Ligand-treated Neonatal Mice Have Increased Innate Immunity Against Intracellular Pathogens and Efficiently Control Virus Infections
J. Exp. Med.,
March 3, 2003;
197(5):
575 - 584.
[Abstract]
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Z.-X. Lian, T. Okada, X.-S. He, H. Kita, Y.-J. Liu, A. A. Ansari, K. Kikuchi, S. Ikehara, and M. E. Gershwin
Heterogeneity of Dendritic Cells in the Mouse Liver: Identification and Characterization of Four Distinct Populations
J. Immunol.,
March 1, 2003;
170(5):
2323 - 2330.
[Abstract]
[Full Text]
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T. Kambayashi, E. Assarsson, A. E. Lukacher, H.-G. Ljunggren, and P. E. Jensen
Memory CD8+ T Cells Provide an Early Source of IFN-{gamma}
J. Immunol.,
March 1, 2003;
170(5):
2399 - 2408.
[Abstract]
[Full Text]
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T. Oida, X. Zhang, M. Goto, S. Hachimura, M. Totsuka, S. Kaminogawa, and H. L. Weiner
CD4+CD25- T Cells That Express Latency-Associated Peptide on the Surface Suppress CD4+CD45RBhigh-Induced Colitis by a TGF-{beta}-Dependent Mechanism
J. Immunol.,
March 1, 2003;
170(5):
2516 - 2522.
[Abstract]
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M. O'Keeffe, H. Hochrein, D. Vremec, B. Scott, P. Hertzog, L. Tatarczuch, and K. Shortman
Dendritic cell precursor populations of mouse blood: identification of the murine homologues of human blood plasmacytoid pre-DC2 and CD11c+ DC1 precursors
Blood,
February 15, 2003;
101(4):
1453 - 1459.
[Abstract]
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A H Lau and A W Thomson
Dendritic cells and immune regulation in the liver
Gut,
February 1, 2003;
52(2):
307 - 314.
[Abstract]
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A. Boonstra, C. Asselin-Paturel, M. Gilliet, C. Crain, G. Trinchieri, Y.-J. Liu, and A. O'Garra
Flexibility of Mouse Classical and Plasmacytoid-derived Dendritic Cells in Directing T Helper Type 1 and 2 Cell Development: Dependency on Antigen Dose and Differential Toll-like Receptor Ligation
J. Exp. Med.,
January 6, 2003;
197(1):
101 - 109.
[Abstract]
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J. L. Miller and E. M. Anders
Virus-cell interactions in the induction of type 1 interferon by influenza virus in mouse spleen cells
J. Gen. Virol.,
January 1, 2003;
84(1):
193 - 202.
[Abstract]
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J. Aliberti, O. Schulz, D. J. Pennington, H. Tsujimura, C. R. e Sousa, K. Ozato, and A. Sher
Essential role for ICSBP in the in vivo development of murine CD8alpha + dendritic cells
Blood,
January 1, 2003;
101(1):
305 - 310.
[Abstract]
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P. Brawand, D. R. Fitzpatrick, B. W. Greenfield, K. Brasel, C. R. Maliszewski, and T. De Smedt
Murine Plasmacytoid Pre-Dendritic Cells Generated from Flt3 Ligand-Supplemented Bone Marrow Cultures Are Immature APCs
J. Immunol.,
December 15, 2002;
169(12):
6711 - 6719.
[Abstract]
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G. Schiavoni, F. Mattei, P. Sestili, P. Borghi, M. Venditti, H. C. Morse III, F. Belardelli, and L. Gabriele
ICSBP Is Essential for the Development of Mouse Type I Interferon-producing Cells and for the Generation and Activation of CD8{alpha}+ Dendritic Cells
J. Exp. Med.,
December 2, 2002;
196(11):
1415 - 1425.
[Abstract]
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A. Krug, R. Uppaluri, F. Facchetti, B. G. Dorner, K. C. F. Sheehan, R. D. Schreiber, M. Cella, and M. Colonna
Cutting Edge: IFN-Producing Cells Respond to CXCR3 Ligands in the Presence of CXCL12 and Secrete Inflammatory Chemokines upon Activation
J. Immunol.,
December 1, 2002;
169(11):
6079 - 6083.
[Abstract]
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B. J. Weigel, N. Nath, P. A. Taylor, A. Panoskaltsis-Mortari, W. Chen, A. M. Krieg, K. Brasel, and B. R. Blazar
Comparative analysis of murine marrow-derived dendritic cells generated by Flt3L or GM-CSF/IL-4 and matured with immune stimulatory agents on the in vivo induction of antileukemia responses
Blood,
December 1, 2002;
100(12):
4169 - 4176.
[Abstract]
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M. O'Keeffe, H. Hochrein, D. Vremec, I. Caminschi, J. L. Miller, E. M. Anders, L. Wu, M. H. Lahoud, S. Henri, B. Scott, et al.
Mouse Plasmacytoid Cells: Long-lived Cells, Heterogeneous in Surface Phenotype and Function, that Differentiate Into CD8+ Dendritic Cells Only after Microbial Stimulus
J. Exp. Med.,
November 18, 2002;
196(10):
1307 - 1319.
[Abstract]
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I. Ferrero, W. Held, A. Wilson, F. Tacchini-Cottier, F. Radtke, and H. R. MacDonald
Mouse CD11c+ B220+ Gr1+ plasmacytoid dendritic cells develop independently of the T-cell lineage
Blood,
September 26, 2002;
100(8):
2852 - 2857.
[Abstract]
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J. M.M. den Haan and M. J. Bevan
Constitutive versus Activation-dependent Cross-Presentation of Immune Complexes by CD8+ and CD8- Dendritic Cells In Vivo
J. Exp. Med.,
September 16, 2002;
196(6):
817 - 827.
[Abstract]
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J. H. Ahn, Y. Lee, C. Jeon, S.-J. Lee, B.-H. Lee, K. D. Choi, and Y.-S. Bae
Identification of the genes differentially expressed in human dendritic cell subsets by cDNA subtraction and microarray analysis
Blood,
August 13, 2002;
100(5):
1742 - 1754.
[Abstract]
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P. Martin, G. M. del Hoyo, F. Anjuere, C. F. Arias, H. H. Vargas, A. Fernandez-L, V. Parrillas, and C. Ardavin
Characterization of a new subpopulation of mouse CD8alpha + B220+ dendritic cells endowed with type 1 interferon production capacity and tolerogenic potential
Blood,
June 28, 2002;
100(2):
383 - 390.
[Abstract]
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M. Gilliet, A. Boonstra, C. Paturel, S. Antonenko, X.-L. Xu, G. Trinchieri, A. O'Garra, and Y.-J. Liu
The Development of Murine Plasmacytoid Dendritic Cell Precursors Is Differentially Regulated by FLT3-ligand and Granulocyte/Macrophage Colony-Stimulating Factor
J. Exp. Med.,
April 1, 2002;
195(7):
953 - 958.
[Abstract]
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