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*
Laboratory of Experimental Immunology, Faculté de Medecine, Universite Libre de Bruxelles, Brussels, Belgium;
Laboratory of Animal Physiology, Institut de Biologie et Medecine Moleculaire, Gosselies, Belgium;
GlaxoSmithKline, Rixensart, Belgium
The induction of dendritic cell (DC) maturation is critical for the
induction of Ag-specific T lymphocyte responses and may be essential
for the development of human vaccines relying on T cell immunity. In
this study, we have investigated the effects of monophosphoryl lipid A
(MPL) on human monocyte-derived DC as well as peripheral blood T cells.
Calcium mobilization, mitogen-activated protein kinase activation, and
the NF-
B transcription factor were induced after MPL stimulation of
DC and required high doses of MPL (100 µg/ml). Maturation parameters
such as production of IL-12 and increases in cell surface expression of
HLA-DR, CD80, CD86, CD40, and CD83 were observed following DC treatment
with MPL. However, lower levels of IL-12 were induced by MPL when
compared with lipopolysaccharide. This is likely to be related to
differences in the kinetics of extracellular signal-related kinase 1/2
and p-38 phosphorylation induced by both molecules. Although maturation
induced by MPL was weaker when compared with lipopolysaccharide, it
appeared to be sufficient to support optimal activation of allogeneic
naive CD45RA+ T cell and anti-tetanus toxoid CD4 T
cells. MPL at low doses (5 µg/ml) had no impact on DC maturation,
while its addition to DC-T cell cocultures induced full T cell
activation. The observed effect was related to the fact that MPL also
acts directly on T cells, likely through their Toll-like receptors, by
increasing their intracellular calcium and up-regulating their CD40
ligand expression. Together, these data support a model where MPL
enhances T cell responses by having an impact on DC and T
cells.
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