慢性移植肾肾病所致功能丧失移植肾切除与否对CD4~+CD25~+Treg细胞的影响

目的 探讨因慢性移植肾肾病(CAN)所致的功能丧失移植肾切除与否对CD4~+ CD25~+调节性T淋巴细胞(Treg细胞)的影响.方法 30例移植肾功能丧失患者,经移植肾活检证实发生CAN,患者群体反应性抗体(PRA)均无增高.根据是否行移植肾切除分为切除组(n=17)和保留组(n=13).两组在原发病构成比、HLA错配及移植后用药等影响机体免疫因素诸方面的差异均无统计学意义.所有受者在移植肾功能丧失后除均服用泼尼松5 mg/d外,近3个月未再服用其他抗排斥反应药物,切除组的患者切除术后仍口服泼尼松5 mg/d,直到术后2个月停用.分别于移植肾切除术前、术后1个月和2个月检测患者外周血单个核细胞中CD4~+ CD25~(high)T淋巴细胞/CD4~+T淋巴细胞(CD4~+ CD25~(high)/CD4~+)比率、细胞毒性T淋巴细胞相关抗原(CTLA-4)表达比率和叉状头螺旋转录因子(Foxp3)表达率.结果 切除组术前CD4~+ CD25~+/CD4~+比率为(1.47±0.19)%,术后2个月为(1.08±0.16)%;保留组相应时间点CD4~+ CD25~(high)/CD4~+比率分别为(1.44±0.25)%和(1.77±0.24)%,切除组术后2个月时CD4~+ CD25~(high)/CD4~+比率明显低于保留组(P<0.01).切除组术前CTLA-4表达比率为(76.82±5.31)%,术后2个月为(72.56±4.99)%;保留组相应时间点CTLA-4表达比率分别为(76.20±4.22)%和(75.24±4.26)%,两组间各时间点的CTLA-4表达比率的差异均无统计学意义(P>0.05).切除组术前Foxp3表达率为(79.77±1.59)%,术后2个月时为(69.07±4.37)%;保留组相应时间点Foxp3表达率分别为(79.56±1.75)%和(79.09±2.05)%,切除组术后2个月时Foxp3表达率明显低于保留组,差异有统计学意义(P<0.01).结论 移植肾切除后CD4~+ CD25~(high)/CD4~+比率及其表面标志性因子Foxp3的表达明显下降,提示移植肾切除可明显抑制CD4~+ CD25~+ Treg的活性.

The change of CD4~+ CD25~+ regulatory T cells after the transplant neplwedamy in human renal redipients with chronic allograft nephropathy

Objective To assess the change of the CD4~+ CD25~+ Treg after the transplant nephrectomy in recipients suffering from chronic allograft nephropathy (CAN) with normal PRA level.Methods Thirty recipients suffering from CAN,aged 20-55 years old,with norlTlal PRA level,were divided into two groups:removal group (n=17) and preserving group(n=13).CD4~+ CD25~(high)/CD4~+,CTLA-4 and Foxp3 in peripheral blood were tested at two time ends:O month and 2 months after the transplant nephrectomy operation.Results (1) Ratio of CD4~+ CD25~(high)/CD4~+ at the Oth and 2nd month in the removal group was(1.47±0.19)%,(1.08±0.16)%,and that was(1.44±0.25)% and (1.77±0.24)%,at the same time in the preserving group (P<0.01).(2) The expression of CTLA-4 at the Oth and 2nd month in the removal group was (76.82±5.31)% and (72.56±4.99)%,and that was (76.20±4.22)% and (75.24±4.26)% in the preserving group (P>0.05).(3)The expression of Foxp3 was (79.77±1.59)% and (69.07±4.37)% in the removal group,and that was (79.56±1.75)% and (79.09±2.05)% in the preserving group.The expression rate of Foxp3 at the 2nd month in the removal group was significantly lower than in the preserving group (P<0.01).Conclusion Remoral of the graft can reduce the ratio of CD4~+ CD25~(high)/CD4~+ and the expression of Foxp3,suggesting that the removal of the renal graft may inhibit the activity of CD4~+ CD25~+ Treg.