Inhibition of rejection in murine islet xenografts by CTLA41g and CD40LIg gene transfer  

作　　者：ZHANG Jian LI Hua JIANG Nan WANG Guo-ying FU Bin-sheng WANG Gen-shu YANG Yang CHEN Gui-hua 

机构地区：[1]J Liver Transplantation Center, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, China

出　　处：《Chinese Medical Journal》2010年第21期3106-3109,共4页中华医学杂志（英文版）

摘　　要：Background Costimulatory signals play a vital role in T cell activation. Blockade of costimulatory pathway by CTLA4Ig or CD40LIg have enhanced graft survival in experimental transplantation models yet mechanisms remain undetermined.We investigated the effects of CTLA4Ig and CD40LIg gene transfer on islet xenografts rejection in rats.Methods Human islets were infected with recombinant adenoviruses containing CTLA4Ig and CD40LIg genes and implanted beneath the kidney capsule of diabetic rats. Levels of blood sugar, morphological changes, and survival of grafts were recorded. Expressions of CTLA4Ig, CD40LIg and insulin were detected by immunohistochemical staining and cytokines levels were quantified by enzyme-linked immunosorbent assay （ELISA）.Results Blood glucose levels in transplant rats decreased to normal level on the 2nd day post transplantation. The mean blood glucose in the control group, CTLA4Ig transfected group, CD40LIg transfected group and CTLA4Ig ＋CD40LIg cotransfected group increased on days 8, 24, 21, 68, post transplantation respectively. The grafts in control group, CTLA4Ig transfected group, CD40LIg transfected group and CTLA4Ig ＋ CD40LIg cotransfected group survived for （8±1）, （29±4）, （27±3）, and （74±10） days, respectively. Survival in CTLA4Ig ＋ CD40LIg cotransfected group was significantly longer. Survivals of CTLA4Ig transfected group and CD40LIg transfected group were significantly longer than control group. In controJ animals, serum interleukin-2 and tumor necrosis factor a concentration significantly increased within seven days post transplantation. Haematoxylin eosin staining of grafts showed live islets in situ of transplant rats without inflammatory cell infiltration. Immunohistochemical staining confirmed the expression of insulin at islets in all experimental groups.Conclusions Transfer of CTLA4Ig and CD40Llg genes, especially the cotransfer of both, inhibits rejection of murine islet xenografts. Downregulated expressions of Th1 cells related cytokines migBackground Costimulatory signals play a vital role in T cell activation. Blockade of costimulatory pathway by CTLA4Ig or CD40LIg have enhanced graft survival in experimental transplantation models yet mechanisms remain undetermined.We investigated the effects of CTLA4Ig and CD40LIg gene transfer on islet xenografts rejection in rats.Methods Human islets were infected with recombinant adenoviruses containing CTLA4Ig and CD40LIg genes and implanted beneath the kidney capsule of diabetic rats. Levels of blood sugar, morphological changes, and survival of grafts were recorded. Expressions of CTLA4Ig, CD40LIg and insulin were detected by immunohistochemical staining and cytokines levels were quantified by enzyme-linked immunosorbent assay （ELISA）.Results Blood glucose levels in transplant rats decreased to normal level on the 2nd day post transplantation. The mean blood glucose in the control group, CTLA4Ig transfected group, CD40LIg transfected group and CTLA4Ig ＋CD40LIg cotransfected group increased on days 8, 24, 21, 68, post transplantation respectively. The grafts in control group, CTLA4Ig transfected group, CD40LIg transfected group and CTLA4Ig ＋ CD40LIg cotransfected group survived for （8±1）, （29±4）, （27±3）, and （74±10） days, respectively. Survival in CTLA4Ig ＋ CD40LIg cotransfected group was significantly longer. Survivals of CTLA4Ig transfected group and CD40LIg transfected group were significantly longer than control group. In controJ animals, serum interleukin-2 and tumor necrosis factor a concentration significantly increased within seven days post transplantation. Haematoxylin eosin staining of grafts showed live islets in situ of transplant rats without inflammatory cell infiltration. Immunohistochemical staining confirmed the expression of insulin at islets in all experimental groups.Conclusions Transfer of CTLA4Ig and CD40Llg genes, especially the cotransfer of both, inhibits rejection of murine islet xenografts. Downregulated expressions of Th1 cells related cytokines mig

关 键 词：transplantation islet of Langerhans CTLA4IG CD40LIg immune tolerance 

分 类 号：S858.28[农业科学—临床兽医学] Q26[农业科学—兽医学]