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*
Immune Cell Biology Program, Stem Cell Biology Branch, Naval Medical Research Institute, Bethesda, MD 20889; and
Uniformed Services University of the Health Sciences, Bethesda, MD 20889
The intracellular signals that mediate the differentiation of
pluripotent hemopoietic progenitors to dendritic cells (DC) are largely
undefined. We have found that the phorbol ester PMA by itself induced
47% ± 8.7% of input human CD34+ hemopoietic
progenitors to differentiate into cells with morphology and surface Ag
phenotype characteristic of DC by day 7 of culture. Functionally,
PMA-generated DC processed and presented whole soluble Ag and also
induced resting T cell proliferation and Ag-specific CTL effector
function. Unlike cytokine-driven DC differentiation, PMA suppressed
proliferation and induced cell death (in part via apoptosis) in cells
that did not differentiate to DC. The effects of PMA were blocked by
inhibitors of protein kinase C activation, suggesting a central role
for this signaling molecule. PMA-mediated signaling also induced
expression of the RelB transcription factor, an NF-
B family member
implicated in DC differentiation. These findings suggest that phorbol
esters activate protein kinase C, which then initiates the terminal
component of an intracellular signaling pathway(s) involved in the DC
differentiation of CD34+ hemopoietic progenitors.
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