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

1997 Fiscal Year Final Research Report Summary

• Project/Area Number: 08671407
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Tohoku University
• Principal Investigator: SUNAMURA Makoto Tohoku University, hospital Reserch Associate, 医学部・附属病院, 助手 (10201584)
• Co-Investigator(Kenkyū-buntansha): KOBARI Masao Tohoku University, School of med.Lecturer, 医学部, 講師 (30170369)
• Project Period (FY): 1996 – 1997
• Keywords: Islet transplantation / IL-12 / anti IL-12 antibody / Th1 / Th2

Research Abstract

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.