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Release by Murine Dendritic Cells1
Department of Medical Microbiology, University of Ulm, Ulm, Germany
Dendritic cells (DC) develop in GM-CSF-stimulated cultures from
murine bone marrow progenitors in serum-free (or low serum) medium.
CD11c+ myeloid DC from 7-day cultures stimulated with
TNF-
, IFN-, IFN-
, or LPS up-regulated surface expression of
CD40 and CD86 costimulator and MHC class II molecules, did not
up-regulate the low "spontaneous" release of IL-18, and did not
release IFN-. Stimulation of in vitro-generated DC with exogenous
IL-12 and IL-18 (but not with IL-4 or LPS plus IL-18) induced IFN-
expression and release in 15–20% of the DC (detectable by FACS
analyses or ELISA). Endogenous IL-12 p70 produced by DC in response to
ligation of CD40 stimulated IFN- release when exogenous IL-18 was
supplied. In vivo-generated, splenic CD8+ and
CD8- DC (from immunocompetent and immunodeficient
H-2d and H-2b mice) cultured with IL-12 and
IL-18 released IFN-. The presence of LPS during the stimulation of
DC with IL-18 plus endogenous (CD40 ligation) or exogenous IL-12 did
not affect their IFN- release. In contrast, splenic
DC pretreated in vitro or in vivo by LPS strikingly down-regulated
IFN- release in response to stimulation by IL-18 and (endogenous or
exogenous) IL-12. Hence, DC are a source of early IFN- generated in
response to a cascade of cytokine- and/or cell-derived signals that can
be positively and negatively regulated.
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