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*
Melbourne Tumor Biology Branch, Ludwig Institute for Cancer Research, Melbourne, Victoria, Australia;
Molecular Genetics and Development Group, Institute of Reproduction and Development, Monash University, Melbourne, Victoria, Australia;
Christchurch Hospital, Christchurch, New Zealand; and
§
Austin Research Institute, Melbourne, Victoria, Australia
This study identifies type I IFNs as activating cytokines in a
serum-free system in which human dendritic cells (DC) were generated
from CD34+ progenitor cells. After 14 days of culture in
GM-CSF, TNF-
, and IL-4, CD34+ progenitors gave rise to a
population of large, immature DC expressing CD1a and CD11b but lacking
CD14, CD80, CD83, CD86, and CMRF44. During the next 2 wk, this
population spontaneously matured into nonadherent,
CD1alow/-, CD11blow/-, CD14-,
CD80+, CD83+, CD86+,
CMRF44+ DC with high allostimulatory activity in the MLR.
To examine which factors influenced this maturation, 25 different
cytokines or factors were added to the immature DC culture. Only type I
IFNs ( or ß) accelerated this maturation in a dose-dependent
manner, so that after only 3 days the majority of large cells acquired
the morphology, phenotype, and function characteristics of mature DC.
Furthermore, supernatants from cultures containing spontaneously
maturing DC revealed low levels of endogenous IFN production. Because
of the similarity of the activation of DC in our culture system with
the phenotypic and functional changes observed during Langerhans cells
activation and migration in vivo, we investigated the effect of IFN-
on human Langerhans cell migration. IFN- also activated the
migration of human split skin-derived DC, demonstrating that this
effect was not limited to DC derived in vitro from hemopoietic
progenitor cells. DC activation by type I IFNs represents a novel
mechanism of immunomodulation by these cytokines, which could be
important during antiviral responses and autoimmune
reactions.
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M. Mohty, A. Vialle-Castellano, J. A. Nunes, D. Isnardon, D. Olive, and B. Gaugler IFN-{alpha} Skews Monocyte Differentiation into Toll-Like Receptor 7-Expressing Dendritic Cells with Potent Functional Activities J. Immunol., October 1, 2003; 171(7): 3385 - 3393. [Abstract] [Full Text] [PDF]
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M. Obuchi, M. Fernandez, and G. N. Barber Development of Recombinant Vesicular Stomatitis Viruses That Exploit Defects in Host Defense To Augment Specific Oncolytic Activity J. Virol., August 15, 2003; 77(16): 8843 - 8856. [Abstract] [Full Text] [PDF]
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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]
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A. Krug, S. Rothenfusser, S. Selinger, C. Bock, M. Kerkmann, J. Battiany, A. Sarris, T. Giese, D. Speiser, S. Endres, et al. CpG-A Oligonucleotides Induce a Monocyte-Derived Dendritic Cell-Like Phenotype That Preferentially Activates CD8 T Cells J. Immunol., April 1, 2003; 170(7): 3468 - 3477. [Abstract] [Full Text] [PDF]
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V. S. Cull, P. A. Tilbrook, E. J. Bartlett, N. L. Brekalo, and C. M. James Type I interferon differential therapy for erythroleukemia: specificity of STAT activation Blood, April 1, 2003; 101(7): 2727 - 2735. [Abstract] [Full Text] [PDF]
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R. Lande, E. Giacomini, T. Grassi, M. E. Remoli, E. Iona, M. Miettinen, I. Julkunen, and E. M. Coccia IFN-{alpha}{beta} Released by Mycobacterium tuberculosis-Infected Human Dendritic Cells Induces the Expression of CXCL10: Selective Recruitment of NK and Activated T Cells J. Immunol., February 1, 2003; 170(3): 1174 - 1182. [Abstract] [Full Text] [PDF]
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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] [Full Text] [PDF]
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M. C. Gauzzi, I. Canini, P. Eid, F. Belardelli, and S. Gessani Loss of Type I IFN Receptors and Impaired IFN Responsiveness During Terminal Maturation of Monocyte-Derived Human Dendritic Cells J. Immunol., September 15, 2002; 169(6): 3038 - 3045. [Abstract] [Full Text] [PDF]
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B. D. Brown and D. Lillicrap Dangerous liaisons: the role of "danger" signals in the immune response to gene therapy Blood, July 30, 2002; 100(4): 1133 - 1140. [Abstract] [Full Text] [PDF]
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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]
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K. Abel, M. J. Alegria-Hartman, K. Rothaeusler, M. Marthas, and C. J. Miller The Relationship between Simian Immunodeficiency Virus RNA Levels and the mRNA Levels of Alpha/Beta Interferons (IFN-{alpha}/{beta}) and IFN-{alpha}/{beta}-Inducible Mx in Lymphoid Tissues of Rhesus Macaques during Acute and Chronic Infection J. Virol., July 17, 2002; 76(16): 8433 - 8445. [Abstract] [Full Text] [PDF]
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M. E. Remoli, E. Giacomini, G. Lutfalla, E. Dondi, G. Orefici, A. Battistini, G. Uze, S. Pellegrini, and E. M. Coccia Selective Expression of Type I IFN Genes in Human Dendritic Cells Infected with Mycobacterium tuberculosis J. Immunol., July 1, 2002; 169(1): 366 - 374. [Abstract] [Full Text] [PDF]
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E. Proietti, L. Bracci, S. Puzelli, T. Di Pucchio, P. Sestili, E. De Vincenzi, M. Venditti, I. Capone, I. Seif, E. De Maeyer, et al. Type I IFN as a Natural Adjuvant for a Protective Immune Response: Lessons from the Influenza Vaccine Model J. Immunol., July 1, 2002; 169(1): 375 - 383. [Abstract] [Full Text] [PDF]
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S. Sasaki, R. R. Amara, W.-S. Yeow, P. M. Pitha, and H. L. Robinson Regulation of DNA-Raised Immune Responses by Cotransfected Interferon Regulatory Factors J. Virol., June 5, 2002; 76(13): 6652 - 6659. [Abstract] [Full Text] [PDF]
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M. Montoya, G. Schiavoni, F. Mattei, I. Gresser, F. Belardelli, P. Borrow, and D. F. Tough Type I interferons produced by dendritic cells promote their phenotypic and functional activation Blood, May 1, 2002; 99(9): 3263 - 3271. [Abstract] [Full Text] [PDF]
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E. Padovan, G. C. Spagnoli, M. Ferrantini, and M. Heberer IFN-{alpha}2a induces IP-10/CXCL10 and MIG/CXCL9 production in monocyte-derived dendritic cells and enhances their capacity to attract and stimulate CD8+ effector T cells J. Leukoc. Biol., April 1, 2002; 71(4): 669 - 676. [Abstract] [Full Text] [PDF]
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 T. Luft, P. Luetjens, H. Hochrein, T. Toy, K.-A. Masterman, M. Rizkalla, C. Maliszewski, K. Shortman, J. Cebon, and E. Maraskovsky IFN-{alpha} enhances CD40 ligand-mediated activation of immature monocyte-derived dendritic cells Int. Immunol., April 1, 2002; 14(4): 367 - 380. [Abstract] [Full Text] [PDF]
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C. Buelens, E. J. Bartholome, Z. Amraoui, M. Boutriaux, I. Salmon, K. Thielemans, F. Willems, and M. Goldman Interleukin-3 and interferon beta cooperate to induce differentiation of monocytes into dendritic cells with potent helper T-cell stimulatory properties Blood, February 1, 2002; 99(3): 993 - 998. [Abstract] [Full Text] [PDF]
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H. Zheng, J. Dai, D. Stoilova, and Z. Li Cell Surface Targeting of Heat Shock Protein gp96 Induces Dendritic Cell Maturation and Antitumor Immunity J. Immunol., December 15, 2001; 167(12): 6731 - 6735. [Abstract] [Full Text] [PDF]
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H. Donaghy, A. Pozniak, B. Gazzard, N. Qazi, J. Gilmour, F. Gotch, and S. Patterson Loss of blood CD11c+ myeloid and CD11c{-} plasmacytoid dendritic cells in patients with HIV-1 infection correlates with HIV-1 RNA virus load Blood, October 15, 2001; 98(8): 2574 - 2576. [Abstract] [Full Text] [PDF]
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T. Luft, M. Rizkalla, T. Y. Tai, Q. Chen, R. I. MacFarlan, I. D. Davis, E. Maraskovsky, and J. Cebon Exogenous Peptides Presented by Transporter Associated with Antigen Processing (TAP)-Deficient and TAP-Competent Cells: Intracellular Loading and Kinetics of Presentation J. Immunol., September 1, 2001; 167(5): 2529 - 2537. [Abstract] [Full Text] [PDF]
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A. E. Morelli, A. F. Zahorchak, A. T. Larregina, B. L. Colvin, A. J. Logar, T. Takayama, L. D. Falo, and A. W. Thomson Cytokine production by mouse myeloid dendritic cells in relation to differentiation and terminal maturation induced by lipopolysaccharide or CD40 ligation Blood, September 1, 2001; 98(5): 1512 - 1523. [Abstract] [Full Text] [PDF]
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F. Mattei, G. Schiavoni, F. Belardelli, and D. F. Tough IL-15 Is Expressed by Dendritic Cells in Response to Type I IFN, Double-Stranded RNA, or Lipopolysaccharide and Promotes Dendritic Cell Activation J. Immunol., August 1, 2001; 167(3): 1179 - 1187. [Abstract] [Full Text] [PDF]
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E. Giacomini, E. Iona, L. Ferroni, M. Miettinen, L. Fattorini, G. Orefici, I. Julkunen, and E. M. Coccia Infection of Human Macrophages and Dendritic Cells with Mycobacterium tuberculosis Induces a Differential Cytokine Gene Expression That Modulates T Cell Response J. Immunol., June 15, 2001; 166(12): 7033 - 7041. [Abstract] [Full Text] [PDF]
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D. H. Libraty, S. Pichyangkul, C. Ajariyakhajorn, T. P. Endy, and F. A. Ennis Human Dendritic Cells Are Activated by Dengue Virus Infection: Enhancement by Gamma Interferon and Implications for Disease Pathogenesis J. Virol., April 15, 2001; 75(8): 3501 - 3508. [Abstract] [Full Text]
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D. Rea, M. J. E. Havenga, M. van den Assem, R. P. M. Sutmuller, A. Lemckert, R. C. Hoeben, A. Bout, C. J. M. Melief, and R. Offringa Highly Efficient Transduction of Human Monocyte-Derived Dendritic Cells with Subgroup B Fiber-Modified Adenovirus Vectors Enhances Transgene-Encoded Antigen Presentation to Cytotoxic T Cells J. Immunol., April 15, 2001; 166(8): 5236 - 5244. [Abstract] [Full Text] [PDF]
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Y.-M. Huang, M. Kouwenhoven, Y.-P. Jin, R. Press, W.-X. Huang, and H. Link Dendritic cells derived from patients with multiple sclerosis show high CD1a and low CD86 expression Multiple Sclerosis, April 1, 2001; 7(2): 95 - 99. [Abstract] [PDF]
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C. Menetrier-Caux, M. C. Thomachot, L. Alberti, G. Montmain, and J. Y. Blay IL-4 Prevents the Blockade of Dendritic Cell Differentiation Induced by Tumor Cells Cancer Res., April 1, 2001; 61(7): 3096 - 3104. [Abstract] [Full Text]
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T. Ito, R. Amakawa, M. Inaba, S. Ikehara, K. Inaba, and S. Fukuhara Differential Regulation of Human Blood Dendritic Cell Subsets by IFNs J. Immunol., March 1, 2001; 166(5): 2961 - 2969. [Abstract] [Full Text] [PDF]
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