Cho D, Lee W J, Halloran P J, Trinchieri G, Kim Y B
Department of Microbiology and Immunology, Finch University of Health Sciences/Chicago Medical School, Illinois 60064, USA.
Cell Immunol. 1996 Aug 25;172(1):29-34. doi: 10.1006/cimm.1996.0211.
These studies describe the effects of recombinant human (rHu) and recombinant murine (rMu) interleukin 12 (IL-12) in the porcine system. To examine the effects of rHu and rMu IL-12, porcine PBL were cultured with rHu and rMu IL-12, and then used for a NK assay. Significant enhancement of porcine NK cell cytotoxicity was observed, and maximal enhancement was reached after 26 hr culture in nanogram quantities (5 ng/ml = 10 units/ml) of rHu and rMu IL-12. Monoclonal antibody (mAb) specific for human IL-12, C8.6, blocked rHu IL-12 enhanced porcine natural killer (NK) cytotoxicity. It was also shown that rHu IL-12 had additive effects on enhancement of NK cell cytotoxicity with PNK-E/G7 mAbs which react with cytolytic trigger molecules on porcine NK cells. By using purified NK cells, porcine tumor necrosis factor-alpha (TNF-alpha) secretion was measured on rHu IL-12 and PNK-E/G7 mAb-activated NK cells. rHu IL-12 and PNK-E/G7 mAbs synergize to induce TNF-alpha secretion. These data indicate that rHu and rMu IL-12 are cross-reactive in the porcine system and suggest the potential use of the porcine system as an important animal model for further study of rHu IL-12.
这些研究描述了重组人(rHu)和重组鼠(rMu)白细胞介素12(IL-12)在猪系统中的作用。为了检测rHu和rMu IL-12的作用,将猪外周血淋巴细胞(PBL)与rHu和rMu IL-12一起培养,然后用于自然杀伤(NK)试验。观察到猪NK细胞细胞毒性显著增强,在以纳克量(5 ng/ml = 10单位/ml)的rHu和rMu IL-12培养26小时后达到最大增强。针对人IL-12的单克隆抗体(mAb)C8.6可阻断rHu IL-12增强的猪自然杀伤(NK)细胞毒性。还显示rHu IL-12与能与猪NK细胞上的溶细胞触发分子反应的PNK-E/G7 mAb对增强NK细胞细胞毒性具有相加作用。通过使用纯化的NK细胞,检测了rHu IL-12和PNK-E/G7 mAb激活的NK细胞上猪肿瘤坏死因子-α(TNF-α)的分泌。rHu IL-12和PNK-E/G7 mAb协同诱导TNF-α分泌。这些数据表明rHu和rMu IL-12在猪系统中具有交叉反应性,并提示猪系统作为进一步研究rHu IL-12的重要动物模型的潜在用途。