[PDF][PDF] CD40 triggering of heterodimeric IL-12 p70 production by dendritic cells in vivo requires a microbial priming signal

O Schulz, AD Edwards, M Schito, J Aliberti… - Immunity, 2000 - cell.com
O Schulz, AD Edwards, M Schito, J Aliberti, S Manickasingham, A Sher, CR e Sousa
Immunity, 2000cell.com
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 …
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.
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