Interleukin-10 modified dendritic cells induce allo-hyporesponsiveness and prolong small intestine allograft survival

摘要

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 × 10⁶ 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 h and 72 h 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 d (P < 0.01), compared with 7.3 ± 2.4 d in control group and 8.3 ± 2.9 d 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.