Toxicological Sciences, Vol 52, 189-198, Copyright © 1999 by Society of Toxicology
KD Coutant, AB de Fraissinette, A Cordier and P Ulrich
For the development of mechanistic assays in immunotoxicology, the
phenotype, cytokine production, and stimulatory function of dendritic cells
(DCs) were assessed after incubation with the chemical haptens aminophenol,
chlorpromazine hydrochloride, dinitrochlorobenzene (DNCB), and with the
DNCB-corresponding tolerogen DCNB, the metal allergen nickel sulfate, the
irritants sodium dodecyl sulfate and benzoic acid, as well as with
staphylococcal enterotoxin B (SEB) and lipopolysaccharide (LPS). DCs were
differentiated from human monocytes by in vitro exposure to GM-CSF and
interleukin-4 (IL-4) for 7 days. Flow cytometric data revealed that only
representative haptens increased the surface expression of HLA-DR, CD86,
CD40, and of CD54 on DCs when compared to irritants or to the tolerogen.
This event was associated with an increased ability of DCs to stimulate T
cell proliferation. Moreover, after incubation with the haptens, but not
with the irritants or the tolerogen, a higher production of TNF-alpha by
DCs was observed. Under our experimental conditions, no release of
IL-1beta, IL-10, or IL-12 was detected. Compared to the activation elicited
by haptens, SEB strongly up-regulated HLA-DR and costimulatory molecule
expression. In agreement with this effect, there was a marked release of
TNF-alpha and a slight production of IL-12. IL-1beta and IL- 10 were not
detected in the culture medium. Finally, SEB-pulsed DCs showed a strong
T-cell-stimulating activity. These data underline the activating potential
of haptens versus irritants or a tolerogen on DC functions. The different
levels of DC activation by haptens and SEB suggested that distinct cellular
events were involved.
ARTICLES
Modulation of the activity of human monocyte-derived dendritic cells by chemical haptens, a metal allergen, and a staphylococcal superantigen
Novartis Pharma, Preclinical Safety, Basel, Switzerland.
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