肝移植患者外周血CD39^+和CD73^+调节性T细胞的表型特点分析

Phenotypic characteristics analysis on CD39 and CD73 in regulatory T cells in the peripheral blood of liver transplantation patients

目的了解肝移植术后患者和健康人群外周血中CD39和CD73在调节性T细胞中的表达特点。方法自2008年6月至2012年12月对76例良性终末期肝病的患者行原位肝移植术,常规术后随访。所有患者肝移植出院后一年内复查外周血CD4+CD25+CD39+T细胞占CD4+CD25+T细胞百分比,同时检测CD4+CD25+CD39+T细胞中FoxP3的百分比,CD4+CD25+CD73+T细胞占CD4+CD25+T细胞百分比,CD4+CD25+CD73+T细胞中FoxP3的百分比,以及CD4+CD25+CD127-T细胞中FoxP3的百分比。检测时患者肝功能良好,无合并感染及新发恶性肿瘤。另选取年龄、性别无统计学差异的60名健康人为健康对照组。结果肝移植术后患者与健康对照组相比,外周血中CD4+CD25+CD39+占CD4+CD25+T细胞的百分比明显降低(P=0.001)。肝移植组与健康对照组外周血绝大多数的CD4+CD25+CD39+T细胞的FoxP3阳性,且两组间FoxP3阳性率无统计学差异[(79.67±7.98)%vs.(82.40±7.01)%,P>0.05]。两组外周血中CD73+占CD4+CD25+T细胞的百分比无统计学差异[(14.97±4.91)%vs.(13.82±4.47)%,P>0.05],大约20%的CD4+CD25+CD73+T细胞FoxP3阳性,且两组间FoxP3阳性率无统计学差异[(18.78±5.53)%vs.(19.19±5.89)%,P>0.05]。两组大约70%的CD4+CD25+CD127-T细胞FoxP3阳性,且两组间FoxP3阳性率无统计学差异[(67.43±6.41)%vs.(69.37±5.15)%,P>0.05]。结论在肝移植患者和健康人群中,CD39+Treg可能是主要发挥免疫调节作用的细胞群,可以作为鉴定Treg细胞的表面标志之一。与健康对照组相比较,外周血CD4+CD25+CD39+Treg细胞在成人肝移植患者中明显降低。

Objective To understand the phenotypic characteristics of CD39 and CD73 in regulatory T cells in the peripheral blood of liver transplantation patients and health individuals. Methods A prospective study compared CD39 and CD73 in regulatory T cells from 76 consecutive benign end-stage liver disease patients who underwent orthotopic liver transplantation from June 2008 to December 2012 to those from 60 age-matched healthy individuals in Department of Transplantation, Second Xiangya Hospital, Central South University and in the Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University. Liver transplant patients provided multiple blood samples during the first year after transplant. Percentages of CD4＋CD25＋CD39＋ T ceils within CD4＋CD25＋T ceils in peripheral blood, FoxP3 within CD4＋CD25＋39＋T cell and percentages of CD4＋CD25＋CD73＋T cells within CD4＋CD25＋T cells, FoxP3 withiri CD4＋CD25＋73＋T cell and FoxP3 within CD4＋CD25＋CD127- T cell were measured. All the patients without infections, hepatitis recurrence or malignancy. Results Compared with the healthy control group, the percentages of CD4＋CD25＋CD39＋within CD4＋CD25＋T cell in peripheral blood of the liver transplant patients was significantly lower （P=0.001）. Most of CD4＋CD25＋ CD39＋T cells in the peripheral blood of liver transplantation group and the healthy control group expressed FoxP3. The positive rate of FoxP3 had no significantly difference between two groups[（79.67±7.98）% vs.（82.40±7.01）%, P〉0.05]. The percentages of CD73＋within CD4＋CD25＋T cell in the peripheral blood of two groups had no significantly difference [（14.97±4.91）% vs. （13.82±4,47）%, P〉0.05], About 20% CD4＋CD25＋ CD73＋T cells expressed FoxP3 and the positive rate of FoxP3 had no significantly difference between two groups [（18.78±5.53）% vs. （19.19±5.89）%, P〉0.05]. About 70% CD4＋CD25＋CD127- T cells expressed FoxP3 of two groups and the positive rate of FoxP3 had no significantly difference between two groups [（67.43±6.41）% vs. （69.37 ±5.15）%, P〉0.05]. Conclusions For the liver transplantation patients and the health individuals, CD39＋ Treg may be the main cell population for immunomodulatory effects and can be regarded as one surface marker to identify Treg cell. Compared with the healthy control group, CD4＋CD25＋CD39＋Treg cells are significantly reduced in the peripheral blood of liver transplantation patients.