负载供肾抗原的受者DC_2细胞对大鼠移植肾的影响

Influence of Renal Transplant Survival in Rats Dendritic Cells(DC_2) Conditioned with Donor Kidney Antigen

【目的】观察负载供肾大鼠抗原的DC2(未成熟DC)在体内特异性抑制急性排斥反应及其对移植物的功能和存活时间的影响。【方法】健康成年BN大鼠65只和Lewis大鼠80只,以BN大鼠为供者,Lewis大鼠为受者。利用受者大鼠骨髓细胞在体外诱导分化为未成熟的淋巴系DC前体细胞(DC2),并对其进行免疫表型分析。将所获得DC2负载供肾大鼠抗原,观察DC2在体外抑制混合淋巴细胞反应(MLR),以及在大鼠同种异体肾移植模型中特异性抑制移植排斥反应发生的情况,Kaplan-Meier生存分析研究对移植大鼠的存活时间的影响。【结果】负载供肾抗原的受者DC2对MLR具有抑制作用(P<0.05);输注负载供肾抗原的DC2实验组的大鼠肾移植术后中位生存时间是62(Q1-Q3:51.1～74.5)d,输注负载无关大鼠抗原和不负载抗原移植的实验组,术后中位生存时间分别是30(Q1-Q3:21.2～37.5)d和27(Q1-Q3:21.0～36.5)d,各实验组与对照组的血清肌酐和细胞因子IFN-γ、IL-4和IL-10的mRNA表达之间的差异具有统计学意义(P<0.05)。【结论】大鼠同系受体来源的负载供肾抗原的DC2具有体外抑制MLR的作用,体内能够预防和抑制急性排斥反应的发生,延长生存时间,提高远期存活率。

【Objective】To observe the specific effect of DC2 conditioned with the donor kidney antigen on inhibition to the acute rejection,graft function and survival time of the recipients.【Methods】A total of 65 adult BN rats（donors） and 80 Lewis rats（recipients） were recruited into the experiment.Immature precursor lymphoid DC（DC2） was prepared with Lewis rats in vitro.The immunophenotype of the DC2 were analyzed subsequently.Then the DC2 we conditioned with donor rats kidney,and its inhibition on mixed lymphocyte reaction（MLR） was observed in vitro.The allogeneic rat kidney transplantation model was further constructed,and its effects of specific inhibition on allograft rejection was observed in vivo.Kaplan-Meier method was used to analyze survival time of the recipients.【Results】The rat kidney antigen conditioned DC2 inhibited MLR（P 0.05）.The median survival time of the rats conditioned with the donor rats kidney antigen after renal transplantation were 62（Q1-Q3：51.1 ～ 74.5） days,but that of the independent kidney antigen conditioned or non-antigen conditioned groups were 30（Q1-Q3：21.2 ～ 37.5） and 27（Q1-Q3：21.0 ～ 36.5） ± 5 days respectively.The peripheral blood creatinine,mRNA expressions of cytokines IFN-γ,IL-4 and IL-10 were statistically different among the experimental group（P 0.05）.【Conclusion】The DC2 conditioned with kidney antigen of the allogeneic donor rat has a key role in inhibiting MLR in vitro,suppressing the occurrence of acute rejection,prolonging the graft＇s survival time and improving the long-term survival rates.