论文部分内容阅读
目的探讨CD4+CD25+Foxp3+调节性T细胞(Treg)联合ICOS单抗在诱导大鼠肝移植免疫耐受中的效果。方法分离Lewis大鼠脾脏Treg后与DA大鼠脾细胞单向混合淋巴细胞反应行体外激活。用“双袖套法”行DA到Lewis的原位肝移植48例。A组为对照组;B、C组分别术前回输体外激活的Treg、术后腹腔注射抗ICOS单抗;D组联合应用Treg和抗ICOS单抗。每组大鼠12只,术后7d各组处死6只受体,检测移植肝组织中Treg的比例及细胞因子水平,观察移植肝病理变化,余大鼠观察生存情况。结果 D组受体生存期[(56.32±10.93)d]明显长于B、C组[(35.17±5.98)d、(33.04±6.39)d](均P<0.05);移植肝组织内Treg的比例[(13.26±3.57)%]也明显高于B、C组(均P<0.05);肝内IL-2水平[(7.25±2.23)ng/L]明显低于A组[(73.02±11.89)ng/L]、B组[(13.10±2.85)ng/L]和C组[(15.66±3.43)ng/L](均P<0.05);但IL-10水平[(57.11±9.27)ng/L]明显高于A组[(26.19±5.25)ng/L]、B组[(33.10±6.73)ng/L]和C组[(30.66±6.23)ng/L](均P<0.05)。结论联合应用ICOS单抗能明显增强Treg对大鼠肝移植急性排斥反应的抑制作用。
Objective To investigate the effect of CD4 + CD25 + Foxp3 + regulatory T cells (Treg) combined with ICOS monoclonal antibody in inducing immune tolerance in rat liver transplantation. Methods The splenic Tregs of Lewis rats were isolated and activated in vitro by one - way mixed lymphocyte reaction with splenocytes of DA rats. Forty-eight patients underwent orthotopic liver transplantation using Lewis’ orthotopic liver transplantation. Group A was control group; group B and group C were preoperatively transfused with Tregs activated in vitro; intraperitoneal injection of anti-ICOS mAbs; Group D combined with Tregs and anti-ICOS monoclonal antibodies. Twelve rats in each group and 6 recipients in each group were sacrificed on the 7th day after operation. The proportion of Tregs and cytokines in the grafted liver tissue were measured. The pathological changes of the liver graft were observed. Survival of the remaining rats was observed. Results The survival time of recipients in group D [(56.32 ± 10.93) d] was significantly longer than that in groups B and C [(35.17 ± 5.98) d, (33.04 ± 6.39) d] (all P <0.05) (13.26 ± 3.57)%] were significantly higher than those in group B and C (all P <0.05). The level of IL-2 in liver was significantly lower than that in group A [(7.02 ± 2.23) ng / L (13.12 ± 2.85) ng / L in group B and 15.66 ± 3.43 ng / L in group B (all P <0.05) L was significantly higher than that in group A [(26.19 ± 5.25) ng / L], group B [(33.10 ± 6.73) ng / L) and group C [(30.66 ± 6.23) ng / L], respectively. Conclusions Combination of ICOS monoclonal antibody can significantly enhance the inhibitory effect of Treg on acute rejection of liver transplantation in rats.