淋巴细胞预输注诱导大鼠移植肝Fas-L表达

Pre-Infusion of Allogeneic Lymphocytes Treated with 5-FU Induced Positive Expression of Fas-L in Rat Liver Graft

目的探讨预输注5-FU处理过的同种异基因淋巴细胞对大鼠移植肝的影响。方法实验分4组,均行Wistar大鼠至SD大鼠的肝移植。对照组:仅行肝移植;单纯淋巴细胞组:受体于术前第7天及第4天各输注Wistar大鼠淋巴细胞(5×106个/ml)悬液1 ml;低浓度5-FU预处理组:受体于术前第7天及第4天各输注经7.5μg 5-FU处理过的Wistar大鼠淋巴细胞(5×106个/ml)悬液1 ml;高浓度5-FU预处理组:受体于术前第7天及第4天各输注经15μg 5-FU处理过的Wistar大鼠淋巴细胞(5×106个/ml)悬液1 ml。于术后第7天处死SD大鼠,行移植肝脏Fas-L及CD8免疫组化检测。结果肝小叶及汇管区中,低浓度5-FU预处理组Fas-L表达阳性细胞的IOD均高于对照组、单纯淋巴细胞组和高浓度5-FU预处理组(P<0.05);单纯淋巴细胞组与高浓度5-FU预处理组比较差异无统计学意义(P>0.05)。肝小叶中,CD8+T淋巴细胞的IOD在单纯淋巴细胞组、低浓度5-FU预处理组和高浓度5-FU预处理组的差异无统计学意义(P>0.05);在汇管区,低浓度5-FU预处理组的CD8+T淋巴细胞IOD低于单纯淋巴细胞组、高浓度5-FU预处理组和对照组(P<0.05)。结论预输注经低浓度5-FU处理的同种异基因淋巴细胞可以较好地诱导大鼠肝移植免疫耐受,其可能的机理是通过诱导移植物中Fas-L表达的上调,从而获得免疫耐受。

Objective To evaluate the effect of pre-infusion of allogeneic lymphoyctes treated with 5-FU on the rat liver graft.Methods Rat liver transplant models from Wistar to SD were established.Four groups were designed as following： control group： only liver transplantation without any other intervention;lymphocytes group： 1 ml of untreated lymphocytes（5×106/ml） from Wistar rats were pre-infused into SD rats on day 7 and 4 separately before transplantation;lymphocytes with low concentration of 5-FU group： low concentration 5-FU（7.5 μg） treated lymphocytes were pre-infused as above;lymphocytes with high concentration of 5-FU group： high concentration 5-FU（15 μg） treated lymphocytes were pre-infused as above.Fas-L and CD8 expression were detected by immunohistochemistry method on day 7 after transplantation.Results The integral opticaldensity（IOD） of Fas-L positive lymphocytes in the lobules of liver and portal areas were higher in lymphocytes with low concentration of 5-FU group than in the other groups（P0.05）.There was no difference between lymphocyte group and lymphocytes with high concentration of 5-FU group（P0.05）.The IOD of CD8＋ expression in lobules of liver was not different among all the three lymphocytes treated groups（P0.05）.But in portal areas,CD8＋ expression was lower in the lymphocytes with low concentration of 5-FU group than in the other groups（P0.05）.Conclusion Pre-infusion of lymphocytes treated with low concentration 5-FU can induce graft immune tolerance,the probable mecanism of which is the increasing Fas-L expression in graft.