Prolongation of Islet allograft by transfection of IL-12, p40 gene into Islet

基于特异性细胞因子的产生将辅助性T细胞亚群分类为Th 1和Th 2群体对于理解各种免疫反应是有用的。IL-12驱动Th 1细胞的发育并抑制Th 2细胞的产生。LL-12在同种异体移植急性排斥反应中的作用尚不清楚。在这项研究中，我们研究了大鼠抗小鼠IL-12单克隆抗体（C 17.8）对小鼠胰岛移植物（ICR* C57 BL/6）存活的影响。术后腹腔内给予C17.8单克隆抗体显著延长胰岛移植物的存活与移植物存活在未经处理的小鼠。未治疗受者的排斥反应的特征是移植物内IFN-γ和IL-2基因表达，而不是IL-4或IL-10，表明Th 1应答。C17.8 mAb治疗在移植后第4、8天损害移植物内Th 1细胞因子（IFN-γ和IL-2）基因表达，并在第4天增强IL-10表达。此外，它减少了移植后体内致敏的脾细胞产生IFN-γ。这些结果表明，移植后全身给予C17.8 mAb可以预防胰岛移植排斥反应，这是由于阻断了Th 1介导的反应。

The classification of T helper cell subsets into Th1 and Th2 populations based on the production of specific cytokines has been useful to understand various immune reactions. IL-12 drives the development of Th1 cells and inhibits the generation of Th2 cells. The role of LL-12 in the acute allograft rejection is still unclear. In this study, we examined the influence of rat anti-mouse-IL-12 mAb (C 17.8) on mouse islet allograft (ICR*C57BL/6) survival. Postoperative intraperitoneal administration of C 17.8 mAb significantly prolonged islet allograft survival as compared with graft survival in untreated mice. The rejection in untreated recipients was characterized by intragraft IFN-gamma and IL-2 gene expressions, not IL-4 or IL-10, indicating Th1 response. C 17.8 mAb therapy impaired intragraft Th1 cytokine (IFN-gamma and IL-2) gene expression on day 4, 8 post-transplant and enhanced IL-10 expression on day 4. Further, it decreased IFN-gamma production from splenocytes in vivo sensitized after transplantation. These findings indicate that post-transplant systemic administration of C 17.8 mAb can prevent islet allograft rejection, which results from the blockade of Th1-mediated response.