title: Cotransfection with IL-10 and TGF-β1 into immature dendritic cells enhances immune tolerance in a rat liver transplantation model.
abstract: Dendritic cells transfected with interleukin (IL)-10 and transforming growth factor-β1 (TGF-β1) enhance T cell immunity and tolerance. However, no quantitative studies have investigated the suppressive functions of immature dendritic cells (imDC) cotransfected with IL-10 and TGF-β1. The effects of imDC cotransfected with IL-10 and TGF-β1 (IL-10-TGF-β1-imDC) on immune tolerance induction in a rat transplantation model were investigated. In addition, effects of IL-10-TGF-β1-imDC relative to IL-10-transfected imDC (IL-10-imDC) and TGF-β1-transfected imDC (TGF-β1-imDC) were compared. The infusion of IL-10-TGF-β1-imDC into recipients prolonged liver graft survival, which was sustained for >90 days. IL-12 serum levels decreased, whereas alanine transaminase and total bilirubin slightly increased in rats infused with IL-10-TGF-β1-imDC compared with the IL-10-imDC and TGF-β1-imDC groups. Furthermore, a higher percentage of terminal transferase-mediated UTP nick end-labeling-positive cells was observed, and histological analysis of the allografts indicated a rejection activity index of mild acute rejection. Our results suggest infusion of IL-10 and TGF-β1 cotransfected imDC induces alloantigen-specific T cell hyporesponsiveness, inhibits antigen-specific immunological responses to liver allografts, prolongs liver allograft survival, and enhances the immune tolerance. This approach may provide a promising alternative for enhancing donor-specific tolerance during liver transplantation.
authors: Department of Pathology, School of Basic Medical Sciences of Fujian Medical University, Fuzhou, Fujian, China;
authors: Lihong
authors: L
authors: Chen
authors: Lin
authors: L
authors: Zheng
authors: Wubing
authors: W
authors: He
authors: Minglian
authors: M
authors: Qiu
authors: Lingyun
authors: L
authors: Gao
authors: Jingfeng
authors: J
authors: Liu
authors: Aimin
authors: A
authors: Huang
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis; D001663:Bilirubin / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*; D015316:Genetic Therapy; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D006085:Graft Survival; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D018664:Interleukin-12 / Q000097:blood; D007519:Isoantigens / Q000276:immunology / Q000378:metabolism; D008099:Liver / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016031:Liver Transplantation / Q000009:adverse effects; D008297:Male; D023421:Models, Animal; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors; D014162:Transfection; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D023001:Transplantation Tolerance
chemical_list: D015415:Biomarkers; C508609:IL10 protein, human; D007519:Isoantigens; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D016753:Interleukin-10; D018664:Interleukin-12; D000410:Alanine Transaminase; D001663:Bilirubin
keywords: dendritic cells; immune tolerance; interleukin-10; liver transplantation; transforming growth factor-β1