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


CONCLUSIONS
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.
Zhu
Min
M
Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China. eming43@hotmail.com
Wei
Ming-Fa
MF
Liu
Fang
F
Shi
Hui-Fen
HF
Wang
Guo
G
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D005434:Flow Cytometry; D015316:Genetic Therapy; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D006085:Graft Survival; D007167:Immunotherapy; D016753:Interleukin-10 / Q000235:genetics*; D007421:Intestine, Small / Q000637:transplantation*; D008081:Liposomes; D051381:Rats; D011920:Rats, Inbred WF; D017207:Rats, Sprague-Dawley; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection; D014184:Transplantation, Homologous
D008081:Liposomes; D016753:Interleukin-10