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Positive Regulatory Role of IL-12 in Macrophages and Modulation by IFN-¹

Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy

Similar to myeloid dendritic cells, murine macrophages and macrophage cell lines were found to express a surface receptor for IL-12. As a result, peritoneal macrophages could be primed by IL-12 to present an otherwise poorly immunogenic tumor peptide in vivo. Using binding analysis and RNase protection assay, we detected a single class of high affinity IL-12 binding sites (K_d of 35 pM) whose number per cell was increased by IFN- via 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 cytokine was tested alone or after priming with IFN- in vitro. In vivo, combined treatment of macrophages with IFN- and IL-12 resulted in synergistic effects on tumor peptide presentation. Therefore, our findings suggest a general and critical role of IL-12 in potentiating the accessory function of myeloid APC.

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