Min Zhu1, Ming-Fa Wei, Fang Liu, Hui-Fen Shi, Guo Wang. 1. Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China. eming43@hotmail.com
Abstract
AIM: To investigate whether IL-10-transduced dendritic cells (DCs) could induce tolerogenicity and prolong allograft survival in rat intestinal transplantation. METHODS: Spleen-derived DCs were prepared and genetically modified by hIL-10 gene. The level of IL-10 expression was quantitated by ELISA. DC function was assessed by MTT in mixed leukocyte reaction. Allogeneic T-cell apoptosis was examined by flow cytometric analysis. Seven days before heterotopic intestinal transplantation, 2 X 10(6) donor-derived IL-10-DC were injected intravenously, then transplantation was performed between SD donor and Wistar recipient. RESULTS: Compared with untransduced DC, IL-10-DC could suppress allogeneic mixed leukocyte reaction (MLR). The inhibitory effect was the most striking with the stimulator/effector (S/E) ratio of 1:10. The inhibition rate was 33.25%, 41.19% (P<0.01) and 22.92% with the S/E ratio of 1:1, 1:10 and 1:50 respectively. At 48 hours and 72 hours by flow cytometry counting, apoptotic T cells responded to IL-10-DC in MLR were 13.8% and 30.1%, while untransduced group did not undergo significant apoptosis (P<0.05). IL-10-DC pretreated recipients had a moderate survival prolongation with a mean allograft survival of 19.8 days (P<0.01), compared with 7.3+/-2.4 days in control group and 8.3+/-2.9 days in untransduced DC group. Rejection occurred in the control group within three days. The difference between untreated DC group and control group was not significant. CONCLUSION: IL-10-DC can induce allogenic T-cell hyporesponsiveness in vitro and apoptosis may be involved in it. IL-10-DC pretreatment can prolong intestinal allograft survival in the recipient.
AIM: To investigate whether IL-10-transduced dendritic cells (DCs) could induce tolerogenicity and prolong allograft survival in rat intestinal transplantation. METHODS: Spleen-derived DCs were prepared and genetically modified by hIL-10 gene. The level of IL-10 expression was quantitated by ELISA. DC function was assessed by MTT in mixed leukocyte reaction. Allogeneic T-cell apoptosis was examined by flow cytometric analysis. Seven days before heterotopic intestinal transplantation, 2 X 10(6) donor-derived IL-10-DC were injected intravenously, then transplantation was performed between SD donor and Wistar recipient. RESULTS: Compared with untransduced DC, IL-10-DC could suppress allogeneic mixed leukocyte reaction (MLR). The inhibitory effect was the most striking with the stimulator/effector (S/E) ratio of 1:10. The inhibition rate was 33.25%, 41.19% (P<0.01) and 22.92% with the S/E ratio of 1:1, 1:10 and 1:50 respectively. At 48 hours and 72 hours by flow cytometry counting, apoptotic T cells responded to IL-10-DC in MLR were 13.8% and 30.1%, while untransduced group did not undergo significant apoptosis (P<0.05). IL-10-DC pretreated recipients had a moderate survival prolongation with a mean allograft survival of 19.8 days (P<0.01), compared with 7.3+/-2.4 days in control group and 8.3+/-2.9 days in untransduced DC group. Rejection occurred in the control group within three days. The difference between untreated DC group and control group was not significant. CONCLUSION:IL-10-DC can induce allogenic T-cell hyporesponsiveness in vitro and apoptosis may be involved in it. IL-10-DC pretreatment can prolong intestinal allograft survival in the recipient.
Authors: Hector A DePaz; Olakunle O Oluwole; Ayotunde O Adeyeri; Piotr Witkowski; Ming-Xing Jin; Mark A Hardy; Soji F Oluwole Journal: Transplantation Date: 2003-02-27 Impact factor: 4.939
Authors: Amy E Anderson; David J Swan; Bethan L Sayers; Rachel A Harry; Angela M Patterson; Alexei von Delwig; John H Robinson; John D Isaacs; Catharien M U Hilkens Journal: J Leukoc Biol Date: 2008-11-06 Impact factor: 4.962