Similar to myeloid dendritic cells, murine macrophages and macrophage cell
lines were found to express a surface receptor for IL-12. As a result, peri
toneal macrophages could be primed by IL-12 to present an otherwise poorly
immunogenic tumor peptide in vivo. Using binding analysis and RNase protect
ion assay, we detected a single class of high affinity IL-12 binding sites
(Kd of similar to 35 pM) whose number per cell was increased by IFN-gamma v
ia up-regulation of receptor subunit expression. Autocrine production of IL
-12 was suggested to be a major effect of IL-12 on macrophages when the cyt
okine was tested alone or after priming with IFN-gamma in vitro. In vivo, c
ombined treatment of macrophages with IFN-gamma and IL-12 resulted in syner
gistic effects on tumor peptide presentation. Therefore, our findings sugge
st a general and critical role of IL-12 in potentiating the accessory funct
ion of myeloid APC.