不同免疫抑制剂对肝移植术后CD4^＋CD25^＋FoxP3^＋调节性T细胞的影响

Effects of different immunosuppressants on peripheral CD4^＋ CD25^＋ FoxP3^＋ regulatory T cells in post liver transplant patients

目的 评价免疫抑制剂对肝移植术后患者外周血CD4^＋ CD25^＋ FoxP3^＋调节性T细胞（regulatory T cell,Treg）的影响.方法 收集肝移植术后6个月以上状态稳定的肝移植患者91例.将患者按使用免疫抑制剂的种类及谷值浓度分为2组,Rapa组8例,FK506组83例,另设正常对照组20例,比较各组患者Treg比例情况.结果 Rapa组患者Treg比例为10.36％±2.52％,FK506组患者Treg比例为6.97％±3.28％,而正常对照组为6.66％±2.41％,Rapa组分别高于FK506组和正常对照组（P=0.004、P=0.005）,但FK506组与正常对照组比较差异无统计学意义（P =0.684）.FK506＜7 ng/ml的低浓度FK506患者65例,Treg比例为7.56％±3.31％,FK506 ≥7 ng/ml高浓度组患者18例,Treg比例为4.84％±2.11％,差异有统计学意义（P=0.001）.直线相关分析显示,FK506谷值浓度与Treg比例间并无直线相关关系（r=-0.119,P=0.284）,但与Treg绝对数量具有直线相关（r =0.307,P=0.005）.结论 肝移植术后长期免疫抑制治疗中,免疫抑制剂对CD4^＋ CD25^＋FoxP3^＋ Treg比例有显著影响.选择合适的免疫抑制剂种类及剂量,有助于提高移植受者体内Treg比例.

Objective To evaluate the effect of immunosuppressants on CD4^＋ CD25^＋ FoxP3^＋ regulatory T cells （Treg） in the peripheral blood of patients post liver transplantation （LT）.Methods A total 91 patients who received LT with steady clinic state for more than 6 months were included.Patients were divided into tacrolimus （FK506） group and rapamycin （Rapa） group according to the type of immunosuppressant.FK506 therapy patients were subdivided into low concentration group （〈 7.0 ng/ml） and high concentration group （≥7.0 ng/ml）.Proportions of CD4^＋ CD25^ ＋ FoxP3^ ＋ Treg in the peripheral blood of recipients were studied among the groups.Results The Treg proportion was 10.36% ± 2.52% in Rapa group （8 cases）.In FK506 group （83 cases）,the Treg proportion was 6.97% ±3.28%.Compared to the proportion of 6.66% ±2.41% in the healthy group,it was higher in Rapa group than that in FK506 group and in healthy group （P =0.004,P =0.005）,respectively.In FK506 group,there were 65 cases on low FK506 concentration group with Treg proportion of 7.56% ± 3.31%.In high concentration group （18 cases）,the proportion of Treg was 4.84% ± 2.11% （P =0.001）.There was no linear correlation between FK506 trough concentration and proportion of Treg （r =-0.119,P =0.284）.However,there was significant correlation between FK506 concentration and the number of Treg （r =0.307,P =0.005）.Conclusions Long-term immuno-suppressive therapy significantly affects the proportion of CD4^ ＋ CD25 ^＋ FoxP3 ^＋ Treg.