Induction of xenogeneic islet transplantation tolerance by simultaneously blocking CD28-B7 and OX40-OX40L co-stimulatory pathways  

作　　者：WANG Guangming FENG Yougang HAO Jie LI Ailing GAO Xiang XIE Shusheng 

机构地区：[1]Department of Immunology,Peking University Health Science Center,Beijing 100083,China

出　　处：《Science China(Life Sciences)》2005年第5期515-522,共8页中国科学(生命科学英文版)

基　　金：This work was supported by the National Natural Science Foundation of China(Grant No.39830340).

摘　　要：It has been demonstrated that prolonged graft survival can be achieved through inhibiting the activation of T cells,and addition of soluble CTLA4Ig and OX40Ig proteins to mixed lymphocyte reactions can effectively inhibit T cell proliferation.To explore the potential of this type of treatment in xenotransplantation,we infected streptozotocin-induced diabetic BalB/c mice(H-2d)(200 mg/kg,IV)with 5×108 pfu AdCTLA4Ig-IRES-OX40Ig on day 1 before islets trans-plantation through the tail vein.The results showed that this treatment prolonged the islet xeno-grafts survival significantly.The reaction to exogenous glucose stimulation was normal and the cytokine secretion of the type Th1 cells was inhibited.The AdCTLA4Ig-IRES-OX40Ig-mediated treatment effectively induced the T cells into anergy and the Th1/Th2 cells into deviation.These results strongly supported the therapeutic potential of blockade of costimulation by Ad-CTLA4Ig-IRES-OX40Ig genes transfer in inducing the organ transplantation tolerance.

关 键 词：CD28-B7 OX40-OX40L STREPTOZOTOCIN ADENOVIRUS islet transplantation Type 1 diabetes mellitus 

分 类 号：N[自然科学总论]