不同免疫抑制剂对肝移植受者外周血中调节性T淋巴细胞比例的影响

目的 探讨西罗莫司(SRL)和钙调磷酸酶抑制剂(CNI)对肝移植受者外周血中CD4+CD25high T淋巴细胞水平的影响.方法 排除肝移植远期移植肝功能异常的受者,将移植肝功能长期(超过2年)稳定的受者47例纳入研究,其中免疫抑制方案使用SRL者15例(SRL组),使用CNI(均为他克莫司)者32例(CNI组).以同期38名健康成人志愿者作为正常对照.使用流式细胞仪检测各组受试者外周血中单个核细胞CD4、CD25及Foxp3的表达水平,比较各组间外周血中CD4+CD25high调节性T淋巴细胞(Treg细胞)的差异.结果 与正常对照组相比,CNI组外周血淋巴细胞中CD4+ CD25high T淋巴细胞的比例显著减少(P<0.05),SRL组CD4+ CD25high T淋巴细胞的比例显著升高(P<0.05).SRL组、正常对照组和CNI组受试者外周血中CD4+ CD25high Foxp3+ Treg 细胞占CD4+ T淋巴细胞的比例依次降低,分别为1.88%(1.56%～2.60%)、1.15%(0.57%～1.48%)和0.84%(0.46%～1.45%),3组间两两比较,差异均有统计学意义(P<0.01或P<0.05).CD4+ CD25 high T淋巴细胞表达Foxp3的阳性率超过95%,CD4+ CD25 low T淋巴细胞表达Foxp3的阳性率低于20%,CD4+ CD25-T淋巴细胞不表达Foxp3.结论 SRL可促进肝移植受者外周血中Treg细胞水平的升高,而CNI可降低Treg细胞的水平.

Rapamycin increased development of CD4+ CD25high Foxp3+T cells of peripheral blood in liver transplant recipients

Objective To investigate the possible influence of immunosuppressive therapy,including sirolimus (SRL) and calcineurin inhibitors (CNI, tacrolimus), on level of Treg in the liver allo-graft recipients, Methods Forty-seven liver transplant recipients with stable liver function were assessed for at least 2 years, and divided into two groups: one composed of 15 patients receiving SRL,and another, of those receiving CNI (32 patients with tacrolimus). Thirty-eight age-matched healthy subjects (HS) were used as normal controls. We examined the expression of CD4, CD25, and Foxp3 in peripheral blood monouclear cells. Treg of every group was analyzed using Cell Quest software.Results SRL significantly increased the prevalence of CD4+ CD25high T cells, compared with HS and CNI group. The prevalence of CD4+ CD25high T cells of CNIs group was significantly lower than that of HS. The percentage of CD4+ CD25high T cells in the total CD4+ T cells was 1.88 % (1.56 %-2. 60 %), 1. 15 % (0. 57 %-l. 48 %) and 0. 84 % (0. 46 %-1. 45 %) in SRL, NS and CNI group,respectively (P<0. 01 or P<0. 05). Foxp3 was expressed in more than 95 % of CD4 + CD25high T cells and less than 20 % of CD4+ CD25low T cells, whereas not expressed in CD4+ CD25- T cells.Conclusion Different immunosuppressive therapy (SRL or CNI) might have different roles in tolerance induction in liver transplant recipients. Namely, SRL promoted the induction of allo-antigen tolerance, but CNI hampered the progression.