Monophosphoryl Lipid A Activates Both Human Dendritic Cells and T Cells

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...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2002-01, Vol.168 (2), p.926-932
Main Authors: Ismaili, Jamila, Rennesson, Joelle, Aksoy, Ezra, Vekemans, Johan, Vincart, Benoit, Amraoui, Zoulikha, Van Laethem, Francois, Goldman, Michel, Dubois, Patrice M
Format: Article
Language:English
Subjects:
Adjuvants, Immunologic - pharmacology
Calcium Signaling - drug effects
Calcium Signaling - immunology
CD28 Antigens - immunology
CD3 Complex - physiology
CD40 Ligand - biosynthesis
CD40L protein
Cell Differentiation - drug effects
Cell Differentiation - immunology
Dendritic Cells - cytology
Dendritic Cells - enzymology
Dendritic Cells - immunology
Dendritic Cells - metabolism
Enzyme Activation - drug effects
Enzyme Activation - immunology
Humans
Immune Sera - pharmacology
Lipid A - analogs & derivatives
Lipid A - pharmacology
Lymphocyte Activation - drug effects
Lymphocyte Activation - immunology
Mitogen-Activated Protein Kinases - metabolism
Monocytes - cytology
monophosphoryl lipid A
Muromonab-CD3 - pharmacology
NF-kappa B - metabolism
T-Lymphocytes - immunology
T-Lymphocytes - metabolism
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Summary: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-kappaB transcription factor were induced after MPL stimulation of DC and required high doses of MPL (100 microg/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 microg/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.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.168.2.926