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The Journal of Immunology, 2001, 167: 221-227.
Copyright © 2001 by The American Association of Immunologists

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

Ursula Grohmann, Maria L. Belladonna, Carmine Vacca, Roberta Bianchi, Francesca Fallarino, Ciriana Orabona, Maria C. Fioretti and Paolo Puccetti2

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 (Kd of ~35 pM) whose number per cell was increased by IFN-{gamma} 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-{gamma} in vitro. In vivo, combined treatment of macrophages with IFN-{gamma} 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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