用负载供体抗原的致耐受性树突状细胞延长大鼠移植肾存活

Prolongation of renal allograft survival with tolerogenic dendritic cells loaded with donor antigen in rats

目的 研究负载供体抗原的致耐受性受体树突状细胞(Dendritic cells,DC)对移植肾存活的影响。方法 以BN、Lewis大鼠为肾移植供、受体;受体骨髓源性DC负载供体淋巴细胞抗原并与共刺激阻断剂CTLA4Ig共孵育;将上述DC于肾移植前24 h经股静脉注入受体(治疗组),未注射DC的受体为对照组;观察各组移植肾存活时间,术后第20天,MTT法检测受体脾细胞对供体及无关抗原刺激的反应。结果移植肾存活时间:与对照组相比,治疗组移植肾存活时间显著延长[(54.6±9.5)d vs(8.3±0.8)d,P<0.01]。术后第20天,治疗组脾细胞对供体抗原刺激的反应明显低于正常对照[(0.17±0.04)vs(0.74±0.06),P<0.01],而受体对无关抗原刺激的反应与正常对照无显著差异[(0.72±0.04)vs(0.69±0.07),P>0.05]。结论 负载供体抗原的致耐受性受体DC可以特异性抑制受体对供体抗原的免疫反应、明显延长大鼠移植肾存活时间。

Objective To study the effects of tolerogenic dendritic cells(DCs) loaded with donor antigen on the survival of renal allografts in rats. Methods Bone marrow-derived DCs of Lewis rats were loaded with antigens from lymphocytes of BN rats and co-cultured with CTLA4Ig to generate tolerogenic DCs loaded with donor antigen. The tolerogenic DCs were injected into the Lewis recipient rats at 24 h before BN to Lewis kidney transplantation (Treatment group) . Survival time of renal allografts was observed and one-way mixed lymphocyte cell reaction(MLR) of the recipients to donors and to the third party lymphocytes was performed by MTT on 20 d after operation. Results Compared with that in the control, the survival time of renal allografts in treatment group was prolonged significantly [(54.6±9.5) d vs (8.3±0.8) d, P <0.0l]. On 20 d, the responsiveness of splenocytes obtained from recipients in treatment group to the antigen stimulation of the donors was significantly lower than that in the control [MLR: (0.17±0.04) vs (0.74± 0.06) , P < 0.01]. No difference was found between the reactions of the recipients and the normal control to the third party. Conclusion Recipient tolerogenic DCs loaded with donor antigen can specifically suppress recipient immune response to donor antigen and significantly prolong the survival of renal allografts.