Abstract
CD40 ligation triggers IL-12 production by dendritic cells (DC) in vitro. Here, we demonstrate that CD40 cross-linking alone is not sufficient to induce IL-12 production by DC in vivo. Indeed, resting DC make neither the IL-12 p35 nor IL-12 p40 subunits and express only low levels of CD40. Nevertheless, after DC activation by microbial stimuli that primarily upregulate IL-12 p40 and augment CD40 expression, CD40 ligation induces a significant increase in IL-12 p35 and IL-12 p70 heterodimer production. Similarly, IL-12 p70 is produced during T cell activation in the presence but not in the absence of microbial stimuli. Thus, production of bioactive IL-12 by DC can be amplified by T cell-derived signals but must be initiated by innate signals.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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3T3 Cells
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Adjuvants, Immunologic / administration & dosage
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Adjuvants, Immunologic / physiology
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Animals
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Antibodies, Monoclonal / administration & dosage
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Antigens, Protozoan / administration & dosage*
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Antigens, Protozoan / immunology*
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CD40 Antigens / biosynthesis
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CD40 Antigens / immunology
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CD40 Antigens / physiology*
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Cells, Cultured
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Dendritic Cells / cytology
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Dendritic Cells / immunology*
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Dendritic Cells / metabolism*
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Dendritic Cells / parasitology
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Dimerization
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Female
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Injections, Intraperitoneal
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Injections, Intravenous
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Interleukin-12 / biosynthesis*
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Interleukin-12 / metabolism
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Interphase / immunology
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Male
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Inbred CBA
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Mice, SCID
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Mice, Transgenic
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Signal Transduction / immunology*
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T-Lymphocytes / immunology
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Toxoplasma / immunology
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Up-Regulation / immunology
Substances
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Adjuvants, Immunologic
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Antibodies, Monoclonal
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Antigens, Protozoan
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CD40 Antigens
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soluble tachyzoite antigen, Toxoplasma gondii
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Interleukin-12