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Malaghan Institute of Medical Research, Wellington School of Medicine, Wellington, New Zealand
The fate of dendritic cells (DC) after they have initiated a T cell
immune response is still undefined. We have monitored the migration of
DC labeled with a fluorescent tracer and injected s.c. into naive mice
or into mice with an ongoing immune response. DC not loaded with Ag
were detected in the draining lymph node in excess of 7 days after
injection with maximum numbers detectable
40 h after transfer. In
contrast, DC that had been loaded with an MHC class I-binding peptide
disappeared from the lymph node with kinetics that parallel the known
kinetics of activation of CD8+ T cells to effector
function. In the presence of high numbers of specific CTL precursors,
as in TCR transgenic mice, DC numbers were significantly decreased by
72 h after injection. The rate of DC disappearance was extremely
rapid and efficient in recently immunized mice and was slower in
"memory" mice in which memory CD8+ cells needed to
reacquire effector function before mediating DC elimination. We also
show that CTL-mediated clearance of Ag-loaded DC has a notable effect
on immune responses in vivo. Ag-specific CD8+ T cells
failed to divide in response to Ag presented on a DC if the DC were
targets of a pre-existing CTL response. The induction of antitumor
immunity by tumor Ag-loaded DC was also impaired. Therefore,
CTL-mediated clearance of Ag-loaded DC may serve as a negative feedback
mechanism to limit the activity of DC within the lymph
node.
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