PMID- 27764710 OWN - NLM STAT- MEDLINE DCOM- 20170915 LR - 20220331 IS - 1872-9142 (Electronic) IS - 0161-5890 (Linking) VI - 79 DP - 2016 Nov TI - Prolonged survival effects induced by immature dendritic cells and regulatory T cells in a rat liver transplantation model. PG - 92-97 LID - S0161-5890(16)30210-3 [pii] LID - 10.1016/j.molimm.2016.10.004 [doi] AB - BACKGROUND: Dendritic cells (DCs) and regulatory T (Treg) cells are crucial for inducing immune tolerance. However, the suppressive function of infused Treg cells and immature DCs (imDCs) following solid organ transplantation remains unclear. METHODS: ImDCs derived from DA-donor rats and Treg cells isolated from spleens of Lewis rats were prepared. A heterotopic liver transplantation model was established to examine the immune tolerance effects of infusion of Treg-imDCs, imDCs and Treg cells individually. Th1/Th2 cytokines and TRAL were detected by ELISA. The overall rejection grade was assessed and the rejection activity index (RAI) was calculated. TUNEL-positive lymphocytes were detected in the portal area in liver sections. RESULTS: The infusion of Treg-imDCs was more effective than imDCs or Treg cells individually. Moreover, the expression of IL-10 and TGF-beta1 was significantly up-regulated, and IL-12 expression was significantly down-regulated, especially in the Treg-imDCs group. The percentage of TUNEL-positive cells was significantly higher in the Treg cells and imDCs groups. The RAI values in Treg-imDCs group on days 3 and 7 were lower than control, imDCs and Treg cells groups individually (p<0.05). Both TBIL and ALT levels in the Treg-imDCs and imDCs groups were significantly lower than those of the control and Treg cells groups, and serum TRAL levels increased significantly 10days after transplantation in the imDC and Treg-imDC groups compared with the control and Treg cells groups (P<0.001). CONCLUSION: These data demonstrated that infusion of Treg cells and/or imDCs induces alloantigen tolerance and prolongs liver allograft survival. The infusion of Treg-imDCs was more effective than imDCs or Treg cells individually. ImDCs synergize with Treg cells in inducing and maintaining the feedback loop between imDCs and Treg cells in vivo. CI - Copyright A(c) 2016 Elsevier Ltd. All rights reserved. FAU - He, Wubing AU - He W AD - Fujian Provincial Hospital, Provincial Clinical Medical College, Fujian Medical University, Fuzhou, Fujian 350001, China. FAU - Chen, Lihong AU - Chen L AD - Department of Pathology, School of Basic Medical Sciences of Fujian Medical University, Fuzhou, Fujian 350004, China; Department of Pathology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian 350025, China. Electronic address: drlhchen@sina.com. FAU - Zheng, Lin AU - Zheng L AD - Department of Pathology, School of Basic Medical Sciences of Fujian Medical University, Fuzhou, Fujian 350004, China. FAU - Luo, Liuping AU - Luo L AD - Department of Pathology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian 350025, China. FAU - Gao, Lingyun AU - Gao L AD - Department of Pathology, School of Basic Medical Sciences of Fujian Medical University, Fuzhou, Fujian 350004, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20161017 PL - England TA - Mol Immunol JT - Molecular immunology JID - 7905289 SB - IM MH - Allografts MH - Animals MH - Dendritic Cells/*immunology/transplantation MH - Disease Models, Animal MH - Enzyme-Linked Immunosorbent Assay MH - Graft Survival/*immunology MH - Immune Tolerance/*immunology MH - In Situ Nick-End Labeling MH - *Liver Transplantation MH - Male MH - Rats MH - Rats, Inbred Lew MH - T-Lymphocytes, Regulatory/*immunology/transplantation OTO - NOTNLM OT - Dendritic cells OT - Immune tolerance OT - Liver transplantation OT - Regulatory T cells EDAT- 2016/10/21 06:00 MHDA- 2017/09/16 06:00 CRDT- 2016/10/21 06:00 PHST- 2016/07/11 00:00 [received] PHST- 2016/10/09 00:00 [revised] PHST- 2016/10/12 00:00 [accepted] PHST- 2016/10/21 06:00 [pubmed] PHST- 2017/09/16 06:00 [medline] PHST- 2016/10/21 06:00 [entrez] AID - S0161-5890(16)30210-3 [pii] AID - 10.1016/j.molimm.2016.10.004 [doi] PST - ppublish SO - Mol Immunol. 2016 Nov;79:92-97. doi: 10.1016/j.molimm.2016.10.004. Epub 2016 Oct 17.