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

通过将IL-12、p40基因转染至胰岛来延长胰岛同种异体移植物

• 批准号: 08671407
• 负责人: SUNAMURA Makoto
• 金额: $ 1.47万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08671407/
• 关键词: Islet transplantation; IL-12; anti IL-12 antibody; Th1; Th2; ICAM-1; LFA-1; IL-12,p40遺伝子; Th2バランス; 血管新生

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.

根据特定细胞因子的产生将 T 辅助细胞亚群分类为 Th1 和 Th2 群体，有助于了解各种免疫反应。 IL-12 驱动 Th1 细胞的发育并抑制 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。在本研究中，我们检测了大鼠抗小鼠 IL-12 mAb (C 17.8) 对小鼠胰岛同种异体移植物 (ICR*C57BL/6) 存活的影响。与未经治疗的小鼠的移植物存活相比，术后腹腔内施用 C 17.8 mAb 显着延长了胰岛同种异体移植物的存活率。未经治疗的受者的排斥反应的特点是移植物内 IFN-γ 和 IL-2 基因表达，而不是 IL-4 或 IL-10，表明 Th1 反应。 C 17.8 mAb 疗法在移植后第 4 天、第 8 天损害了移植物内 Th1 细胞因子（IFN-γ 和 IL-2）基因表达，并在第 4 天增强了 IL-10 表达。此外，它还减少了移植后体内致敏的脾细胞产生的 IFN-γ。这些发现表明，移植后全身施用 C 17.8 mAb 可以预防胰岛同种异体移植排斥，这是由于 Th1 介导的反应被阻断而导致的。