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Blood, 1 August 2001, Vol. 98, No. 3, pp. 736-742
IMMUNOBIOLOGY
Type I interferons in combination with bacterial stimuli induce
apoptosis of monocyte-derived dendritic cells
Manfred Lehner,
Thomas Felzmann,
Katharina Clodi, and
Wolfgang Holter
From the Children's Cancer Research Institute (CCRI),
St Anna Children's Hospital, Vienna, Austria.
Both type I interferons (IFNs) as well as lipopolysaccharide (LPS)
individually compromise selected monocytic or dendritic cell (DC)
functions. This study investigates the influence of these agents on the
differentiation and the regulation of cell death of monocyte-derived
DCs generated in the presence of granulocyte-macrophage colony-stimulating factor plus interleukin-4 (IL-4). It is reported that excessive apoptosis occurred rapidly in monocyte-derived DC
cultures, if IFN- or IFN- was added in combination with LPS or
lipoteichoic acid (LTA). The small fraction of cells surviving in such
cultures displayed a mature DC phenotype with expression of CD83, CD80,
and CD86. IL-10 was found in the supernatants of monocyte-derived DC
cultures, if supplemented with LPS or IFN- plus LPS but not in
control cultures. When monocyte-derived DCs were generated in the
presence of IFN- without LPS, these cells displayed an immature DC
phenotype with a reduction of cell recovery but no overt apoptosis.
However, the addition of LPS, LTA, LPS plus IFN- , or tumor necrosis
factor (TNF-) plus prostaglandin E2 to such cells again resulted
in the rapid induction of apoptosis in the majority of cells, together
with a reduced production of IL-12 p70 and TNF-. Together, these
data indicate an exquisite sensitivity of monocyte-derived DCs to
activation-induced cell death if generated in the presence of IFN-,
indicating the existence of an important mechanism of immunosuppression
caused by IFN--inducing agents, such as viral or bacterial stimuli.
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