Administration of dendritic cells dual expressing DcR3 and GAD65 mediates the suppression of T cells and induces long-term acceptance of pancreatic-islet transplantation.
Pancreatic-islet transplantation is currently regarded as the only approach to cure type 1 diabetic patients (T1D). However, recurrent autoimmunity is a critical factor contributing to graft rejection along with alloreactivity. Recently, the glutamic acid decarboxylase 65 (GAD65) was identified as the one of the major pancreatic antigens targeted by self-reactive T cells in T1D. Therefore, the T cells specific for GAD65 may be the important therapeutical target of T1D. In this study, dendritic cells (DCs) were transfected with the recombinant adenovirus, dual expressing DcR3 and GAD65 in vitro, and NOD mice were administrated with the genetically modified DCs in vivo after islet transplantation. The results demonstrated that the genetically modified DCs significantly suppressed the T cell response to GAD65, delayed onset of diabetes, improved the success and survival of islet transplantation. The findings suggest that the adoptive transfer of genetically modified DCs dual expressing DcR3 and GAD65 represent a future therapeutic potential in T1D and pancreatic-islet transplantation.
Li
Qiansheng
Q
Department of Urology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
Ge
Chengguo
C
Liu
Rongrong
R
Zhang
Keqin
K
Wu
Gang
G
Huo
Wenqian
W
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005822:Genetic Vectors; D005968:Glutamate Decarboxylase / Q000096:biosynthesis*; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007108:Immune Tolerance; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D051379:Mice; D016688:Mice, Inbred NOD; D053323:Receptors, Tumor Necrosis Factor, Member 6b / Q000096:biosynthesis*; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection
D053323:Receptors, Tumor Necrosis Factor, Member 6b; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2