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

根据特定细胞因子的产生将辅助性T细胞亚群分为Th1和Th2群，有助于了解各种免疫反应。IL-12驱动Th1细胞的发育，抑制Th2细胞的生成。LL-12在急性同种异体移植排斥反应中的作用尚不清楚。在这项研究中，我们检测了大鼠抗小鼠il -12单抗（c17.8）对小鼠胰岛移植（ICR*C57BL/6）存活的影响。与未处理的小鼠相比，术后腹腔注射c17.8 mAb可显著延长同种异体胰岛移植存活时间。未治疗受体的排斥反应以ifn - γ和IL-2基因表达为特征，而不是IL-4或IL-10，表明Th1应答。c17.8 mAb治疗在移植后第4天和第8天损伤了移植体内Th1细胞因子（ifn - γ和IL-2）基因的表达，并在第4天增强了IL-10的表达。此外，它减少了移植后致敏的脾细胞体内ifn - γ的产生。这些发现表明，移植后全身给药c17.8 mAb可以防止胰岛移植排斥反应，这是由于阻断th1介导的反应造成的。

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.