Positive regulatory role of IL-12 in macrophages and modulation by IFN-gamma

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.