[Experimental study on immune tolerance induced by human Ad-CTLA-4Ig in rats with pancreaticoduodenal transplantation].
OBJECTIVE
To study the immune tolerance induced by human Ad-CTLA-41g after pancreaticoduodenal transplantation of rats.


METHODS
Wistar rats with diabetes were induced by caudal intravenous administration of streptozotocin (STZ) at a single dose of 60 mg/kg. Pancreaticoduodenal transplantations were performed with the SD rats as donors and the diabete Wistar rats as recipients. The SD pancreaticoduodenal grafts with human Ad-CTLA-41g infection via arterial perfusion in vitro were transplanted into Wistar rats with diabetes. The blood glucose of the rats was measured after transplantation. The graft functional survival time (GFST) was recorded. The concentration of IL-2 was measured by ELISA on day 3 and day 10 after operation. The human CTLA-41g was detected by Western blot after operation.


RESULTS
The GFST of control group without gene transfer was (11+/- 1) d, while that of gene transfer group was (33 +/-4) d (P< 0. 01). The expression of serum human CTLA-41g was detected in rats of gene transfer group on the 10th day after transplantation, while no serum human CTLA-4Ig was detected in rats of control group without gene transfer. On the 3rd day after transplantation, the level of serum IL-2 was (33. 710+/-7. 803) pg/mL in rats of transfer group, and was (44. 772+/-9. 102) pg/mL in rats of control group without gene transfer. On the 10th day, the level of serum IL-2 was (47. 846+/-14. 050) pg/mL in rats of transfer group, and was (80. 806+/-18. 629) pg/mL in rats of control group without gene transfer. The levels of serum IL-2 in rats of transfer group was much lower than those of the control group without gene transfer (P<O. 01).


CONCLUSIONS
In vitro perfusion with human Ad-CTLA-41g is an effective method to transfer the target gene into pancreaticoduodenal graft. Ad-CTLA-41g infection can induce immune tolerance in rat with pancreaticoduodenal transplantation.
Meng
Ling-xiang
LX
Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, China.
Hu
Wei-ming
WM
Zhang
Zhao-da
ZD
Han
Fang-hai
FH
Zhou
Xiang
X
Jia
Wei
W
Lu
Hui-min
HM
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D015703:Antigens, CD / Q000235:genetics*; D001786:Blood Glucose / Q000378:metabolism; D060908:CTLA-4 Antigen; D004386:Duodenum / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics*; D007136:Immunoglobulins / Q000235:genetics*; D007376:Interleukin-2 / Q000378:metabolism; D008297:Male; D010179:Pancreas / Q000276:immunology* / Q000378:metabolism; D016035:Pancreas Transplantation / Q000276:immunology*; D051381:Rats; D015996:Survival Rate
D015703:Antigens, CD; D001786:Blood Glucose; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C556708:Ctla4 protein, rat; D007136:Immunoglobulins; D007376:Interleukin-2