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Department of Experimental Medicine, University of Perugia, Perugia, Italy
Ligation of CD40 on dendritic cells (DC) triggers production of
IL-12. Using an adoptive transfer model we have previously shown that
rIL-12 acts directly on DC to enhance presentation of an otherwise
poorly immunogenic tumor peptide. Using the same experimental model, we
now describe a similar adjuvanticity of CD40 ligation on peptide
presentation by DC. We also explore the possibility that the IL-12
resulting from CD40 ligation directly affects the APC function of DC,
mediating or contributing to the adjuvant effect of CD40 ligation. CD40
engagement in vitro and rIL-12 at concentrations in the range induced
by CD40 ligation were equally effective in priming DC for presentation
of the tumor peptide in vivo. Remarkably, the copresence in vitro of
neutralizing Ab to IL-12, but not to TNF-
, IL-1ß, or IFN-
,
ablated the enhancing effect of CD40 engagement on the APC function of
DC. These data suggest a major role for autocrine IL-12 in DC
modulation via CD40 ligation.
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