Adenoviral-mediated localized CTLA-4Ig gene expression induces long-term allograft pancreas survival and donor-specific immune tolerance in rats  

作　　者：Chen Xianhua John Huang 

机构地区：[1]Health Branch, Southwest Hospital, Third Military Medical University, Chongqing 400038, China [2]Department of Medicine, University of California, San Francisco, CA 94143-0780, USA

出　　处：《Journal of Medical Colleges of PLA(China)》2008年第6期313-323,共11页中国人民解放军军医大学学报（英文版）

摘　　要：T cell activation following alloantigen recognition plays a critical role in the development of the rejection in all solid organ, tissue and cell transplantation. A recombinant molecule, cytotoxic T lymphocyte antigen 4 antibody （CTLA-4Ig）, is known to induce to T-cell into ＂anergy＂ by blocking the costimulatory B7-CD28 interaction. Either systemic or localized administration of CTLA-Ig has been shown to prolong allograft survival and induce donor-specific tolerance in some transplant models. In this study, we characterized the expression and immunosuppressive effectiveness of adenoviral-mediated CTLA-4Ig gene transfer. We demonstrated transduction of the allografts with AdCTLA-4Ig resulted in localized expression, permanent graft survival and stable donor-specific tolerance. In addition, by performing simultaneous dual-organ through a local expression of CTLA-4Ig via adenoviral-mediated transplantation, we targeted on immunosuppression gene transfer into pancreatic allografts.T cell activation following alloantigen recognition plays a critical role in the development of the rejection in all solid organ, tissue and cell transplantation. A recombinant molecule, cytotoxic T lymphocyte antigen 4 antibody (CTLA-4Ig), is known to induce to T-cell into "anergy" by blocking the costimulatory B7-CD28 interaction. Either systemic or localized administration of CTLA-Ig has been shown to prolong allograft survival and induce donor-specific tolerance in some transplant models. In this study, we characterized the expression and immunosuppressive effectiveness of adenoviral-mediated CTLA-4Ig gene transfer. We demonstrated transduction of the allografts with AdCTLA-4Ig resulted in localized expression, permanent graft survival and stable donor-specific tolerance. In addition, by performing simultaneous dual-organ transplantation, we targeted on immunosuppression through a local expression of CTLA-4Ig via adenoviral-mediated gene transfer into pancreatic allografts.

关 键 词：Cytotoxic Tlymphocyte antigen 4 antibody Immunosuppression Tolerance Diabetes ADENOVIRUS Gene transfer Pancreatic transplantation 

分 类 号：R587.1[医药卫生—内分泌]