负载供肾抗原的致耐受性树突状细胞延长大鼠移植肾存活时间

Prolongation of renal allografts survival in rats by tolerogenic recipient dendritic cells loaded with donor renal antigen

目的探讨负载供肾抗原的致耐受性受者树突状细胞(DCs)对移植肾存活时间的影响。方法以BN大鼠为供者,Lewis大鼠为受者,Wistar大鼠为无关供者。将受者的骨髓分离培养,未经其它处理得到的DCs,将其作为DCs1;DCs1经CTLA-4Ig基因重组的复制缺陷型腺病毒(AdvCTLA-4Ig)转染后作为DCs2;DCs1先经BN大鼠供肾抗原负载后再进行AdvCTLA-4Ig转染,作为DCs3。将受者随机分为DCs1、DCs2、DCs3及对照组,每组6只。术前24h,前3组分别注入1×106个DCs1、DCs2和DCs3,对照组不注射DCs。肾移植后观察各组移植肾存活时间,术后第20d检测受者脾细胞对负载供肾抗原及无关供者肾脏抗原DCs的反应。结果DCs1、DCs2,DCs3和对照组的移植肾存活时间分别为(8.1±0.8)d、(8.8±0.9)d、(62.1±13.7)d和(8.6±0.9)d。DCs1、DCs2组与对照组比较,差异无统计学意义(P>0.05),DCs3组与对照组比较,移植肾存活时间显著延长(P<0.01)。肾移植术后,DCs3组脾细胞对负载供肾抗原的DCs反应明显低于对照组(P<0.01),而对负载无关供者抗原的DCs反应与对照组比较,差异无统计学意义(P>0.05)。结论负载供肾抗原的受者DCs经CTLA-4Ig基因修饰后具有致耐受性,可以抑制受者对供者抗原的免疫反应,明显延长移植肾的存活时间。

Objective To study the influence of recipient tolerogenic dendritic cells （DCs） loaded with donor renal antigen on renal allografts survival in rats. Methods Bone marrow derived DCs of Lewis rats were loaded with antigens from donor kidney of BN rats and transferred with AdvCTLA4Ig to generate tolerogenic DCs. The tolerogenic DCs were injected into the Lewis recipient 24 h before BN→Lewis kidney transplantation （treatment group）. Survival time of renal allografts was observed and splenic cell reaction of the recipients to donors and the third party antigens were assayed by means of MTF on the 20^th postoperative day. Results Survival time of renal allografts in treatment group was prolonged significantly as compared with controls （62. 1 ± 13.7 days vs 8. 6±0. 9 days, P 〈0. 01）. On the day 20, the recipients in treatment group showed significant hyporesponsiveness to donor antigen, but normal reaction to the third party. Conclusion Recipient DCs loaded with donor renal antigen are rendered tolerogenic by modification with CTLA-4Ig gene, can suppress recipients immune response to donor antigen specifically and prolong the survival of renal allografts significantly.