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* Hepatobiliary Service, Memorial Sloan-Kettering Cancer Center, New York, NY 10021; and
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
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 x 108 cells. DC numbers remained substantially
elevated even 75 days after treatment. The DC population was either
CD8
+CD4- or
CD8-CD4- but not
CD8+CD4+ or
CD8-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- 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-
. 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-. 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.
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