Positive regulatory role of IL-12 in macrophages and modulation by IFN-γ
Positive regulatory role of IL-12 in macrophages and modulation by IFN-γ
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DOI：
10.4049/jimmunol.167.1.221
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发表时间：
2001-07-01
影响因子：
4.4
通讯作者：
Puccetti, P
中科院分区：
文献类型：
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作者：
Grohmann, U;Belladonna, ML;Puccetti, P
与髓样树突状细胞类似，发现鼠巨噬细胞和巨噬细胞系表达IL-12的表面受体。结果，腹腔巨噬细胞可以被IL-12引发以在体内呈递否则免疫原性差的肿瘤肽。使用结合分析和RNase保护测定，我们检测到一类高亲和力IL-12结合位点（Kd类似于35 pM），其数量/细胞通过IFN-γ上调受体亚基表达而增加。IL-12的自分泌产生被认为是IL-12对巨噬细胞的主要作用，当细胞因子单独测试或在体外用IFN-γ引发后测试时。在体内，用IFN-γ和IL-12联合处理巨噬细胞导致对肿瘤肽呈递的协同作用。因此，我们的研究结果表明IL-12在增强骨髓APC的辅助功能中具有普遍和关键的作用。
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 similar to 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.