肝移植急性排异患者外周血Th17及调节性T细胞的特征及意义

目的 探讨肝移植术后急性排异患者外周血中Th17细胞、CD4+CD25+Foxp3+调节性T细胞(Treg)的变化特征及临床意义.方法 2011年1-9月解放军302医院肝移植研究中心收治的肝移植术后患者25例,根据移植组织穿刺活检病理结果分为急性排异组(排异组,12例)和非排斥稳定组(稳定组,13例),另选取13名健康体检者作为对照.采用流式细胞分析法检测外周血中Th17、Treg细胞占CD4+T细胞的比例,观察Th17/Treg比值变化及其与肝脏损伤的关系.结果移植术后排异组外周血中Th17占CD4+T细胞的比例(3.50％±0.86％)明显高于稳定组(2.10％±0.52％)和对照组(1.79％±0.42％,P＜0.01),稳定组和对照组比较无统计学差异(P＞0.05).排异组和稳定组患者外周血中Treg占CD4+T细胞的比例(分别为0.90％±0.25％、1.51％±0.23％)明显低于对照组(2.57％±0.79％,P＜0.01),且排异组明显低于稳定组(P＜0.05).排异组Th17/Treg比值(4.20±1.69)明显高于稳定组(1.43±0.47)及对照组(0.75±0.28,P＜0.01),且稳定组明显高于对照组(P＜0.01).Th17/Treg比值与丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、碱性磷酸酶(ALP)、谷氨酸转氨酶(GGT)水平呈正相关(分别为r=0.5023,P=0.0105; r=0.4561,P=0.0219;r=0.4393,P=0.0280; r=0.5516,P=0.0043).结论 肝移植术后急性排异反应患者外周血中存在Th17/Treg失衡,且与肝脏损伤有一定关系.Th17/Treg失衡可能参与了肝移植术后急性排异反应的发生发展过程.

Characteristics and significance of peripheral blood Th17 cells and regulatory T cells in liver transplantation patients with acute rejection

Objective To investigate the characteristics of changes and clinical significance of Th17 cells and CD4+CD25+Foxp3+ regulatory T cells(Treg) in peripheral blood in liver transplant patients suffering from acute transplant rejection.Methods A total of 25 liver transplant patients admitted in 302 Hospital of People’s Liberation Army from January to September 2011 underwent needle biopsy for the transplanted hepatic tissue.The patients were divided into two groups: acute rejection group(12 cases) and stable-graft group(13 cases).In addition,13 healthy people were enlisted in the study and regarded as control.Flow cytometric analysis was used to measure the proportion of Th17 cells and Treg cells in peripheral blood among CD4+ T cells,and to observe the relationship between change in Th17/Treg ratio and liver injury.Results The proportion of Th17/CD4+T in acute rejection group(3.50%±0.86%) after transplantation was higher than that in the stable-graft group(2.10%±0.52%) and control group(1.79%±0.42%,P<0.01).There was no statistical difference in cell ratio between the stable-graft group and control group(P>0.05).The Treg/CD4+T cell ratio in the peripheral blood of the patients from acute rejection and stable-graft group(0.90%±0.25% and 1.51%±0.23%,respectively) were significantly lower than that of control group(2.57%±0.79%,P<0.01),and that of acute rejection group was notably lower than that of stable-graft group(P<0.05).The Th17/Treg ratio in acute rejection group(4.20±1.69) was significantly higher than that of stable-graft group(1.43±0.47) and control group(0.75±0.28,P<0.01),and that of stable-graft group was higher than that of control group(P<0.01).The ratio of Th17/Treg was positively correlated with alanine aminotransferase(ALT),aspartate aminotransferase(AST),alkaline phosphatase(ALP),and glutamate transaminase(GGT) levels(r=0.5023,P=0.0105;r=0.4561,P=0.0219;r=0.4393,P=0.0280;and r=0.5516,P=0.0043,respectively).Conclusions Th17/ Treg imbalance exists in liver transplant patients suffering from acute rejection,which may be related to liver injury to a certain degree.Furthermore,Th17/Treg imbalance may be involved at the onset and development of acute rejection after liver transplantation.