Endogenous granulocyte-macrophage colony-stimulating factor overexpression in vivo results in the long-term recruitment of a distinct dendritic cell population with enhanced immunostimulatory function Journal Article


Authors: Miller, G.; Pillarisetty, V. G.; Shah, A. B.; Lahrs, S.; Xing, Z.; DeMatteo, R. P.
Article Title: Endogenous granulocyte-macrophage colony-stimulating factor overexpression in vivo results in the long-term recruitment of a distinct dendritic cell population with enhanced immunostimulatory function
Abstract: GM-CSF is critical for dendritic cell (DC) survival and differentiation in vitro. To study its effect on DC development and function in vivo, we used a gene transfer vector to transiently overexpress GM-CSF in mice. We found that up to 24% of splenocytes became CD11c+ and the number of DC increased up to 260-fold to 3 × 108 cells. DC numbers remained substantially elevated even 75 days after treatment. The DC population was either CD8α+CD4- or CD8α-CD4- but not CD8α+CD4+ or CD8α-CD4+. This differs substantially from subsets recruited in normal or Flt3 ligand-treated mice or using GM-CSF protein injections. GM-CSF-recruited DC secreted extremely high levels of TNF-α compared with minimal amounts in DC from normal or Flt3 ligand-treated mice. Recruited DC also produced elevated levels of IL-6 but almost no IFN-γ. GM-CSF DC had robust immune function compared with controls. They had an increased rate of Ag capture and caused greater allogeneic and Ag-specific T cell stimulation. Furthermore, GM-CSF-recruited DC increased NK cell lytic activity after coculture. The enhanced T cell and NK cell immunostimulation by GM-CSF DC was in part dependent on their secretion of TNF-α. Our findings show that GM-CSF can have an important role in DC development and recruitment in vivo and has potential application to immunotherapy in recruiting massive numbers of DC with enhanced ability to activate effector cells.
Keywords: controlled study; nonhuman; cd8 antigen; t-lymphocytes; mouse; animals; mice; animal tissue; cell survival; gene overexpression; spleen; dendritic cell; cell line; animal experiment; animal model; gene function; in vivo study; tumor cells, cultured; cell population; mice, inbred balb c; mice, inbred c57bl; gene transfer; viral gene delivery system; genetic vectors; colorectal neoplasms; lymphocyte activation; dendritic cells; tumor necrosis factor alpha; immunotherapy; antigens; tumor necrosis factor-alpha; gamma interferon; antigen specificity; t-lymphocytes, cytotoxic; melanoma, experimental; interleukin 6; cell movement; natural killer cell; killer cells, natural; cytokine production; cytolysis; cytotoxicity, immunologic; immunophenotyping; cell count; immunostimulation; adenovirus vector; cd4 antigen; adjuvants, immunologic; cell stimulation; cytokine release; cell activity; injections, intravenous; adenoviridae; spleen cell; coculture techniques; immunopharmacology; cd11 antigen; granulocyte-macrophage colony-stimulating factor; granulocyte macrophage colony stimulating factor receptor; dna vector; humans; male; priority journal; article
Journal Title: Journal of Immunology
Volume: 169
Issue: 6
ISSN: 0022-1767
Publisher: The American Association of Immunologists, Inc  
Date Published: 2002-09-15
Start Page: 2875
End Page: 2885
Language: English
PUBMED: 12218100
PROVIDER: scopus
DOI: 10.4049/​jimmunol.169.6.2875
DOI/URL:
Notes: Export Date: 14 November 2014 -- Source: Scopus
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MSK Authors
  1. George Miller
    18 Miller
  2. Ronald P DeMatteo
    635 DeMatteo
  3. Alaap Shah
    20 Shah
  4. Svenja   Lahrs
    9 Lahrs