使用他克莫司的肝移植受者T淋巴细胞亚群及CD28家族共刺激分子的分析

Analysis of T lymphocyte subgroups and CD28-family co-stimulators in allo-liver recipients receiving tacrolimus treatment

目的观察使用他克莫司（Tac）的肝移植受者外周血中T淋巴细胞亚群及CD28家族共刺激分子表达的变化及其意义。方法以接受同种异体肝移植的受者20例为Tac组，术后采用Tac、霉酚酸酯（或硫唑嘌呤）和糖皮质激素预防排斥反应；以等待肝移植的终末期肝脏疾病患者20例为肝病对照组；以健康志愿者20名为正常对照组。测定正常对照组志愿者和肝病对照组患者的外周血中T淋巴细胞亚群及其CD28、可诱导共刺激分子（ICOS）、CD152和程序性死亡因子1（PD-1）的表达；分别测定Tac组使用Tac后2周、1个月、2个月和3个月时外周血中T淋巴细胞亚群及其CD28、ICOS、CDl52和PD-1的表达。结果肝病对照组、正常对照组和Tac组各时点间的CD3’T淋巴细胞的差异无统计学意义（P〉O．05）。随着使用Tac时间的延长，Tac组CD4’T淋巴细胞持续下降，至使用Tac3个月时，明显低于正常对照组（P〈O．05）；CD8^＋T淋巴细胞逐渐增加至正常水平。Tac组T淋巴细胞亚群表面ICOS分子表达持续低于正常对照组（P〈0．05），CD4’T淋巴细胞表面CD28分子表达恢复至正常水平（P〉0．05），而CD8’T淋巴细胞表面CD28分子持续低表达（P〈O．05）。同时，Tac组T淋巴细胞亚群表面CDl52分子和PD-1分子的表达均持续高于正常对照组（P〈0．05）。结论肝移植患者接受以Tac为主的免疫抑制治疗，其T淋巴细胞亚群平衡紊乱得到纠正，T淋巴细胞亚群表面CD28分子和ICOS分子的表达下调，CD152分子和PD-1分子的表达上调，通过共刺激信号的调节来达到抑制排斥反应的目的。

Objective To observe the change and significance of peripheral T lymphoctye subgroups and the expression of CD28-family co-stimulators in allo-liver recipients receiving Tacrolimus （Tac）-treatment. Methods Twenty allo-liver recipients who took Tac, mycophenolic acid （MPA） and glucocorticoid to prevent rejection after transplantation served as Tac group; 20 patients with terminal-stage hepatic diseases and waiting for liver transplantation as hepatic-disease-control group; 20 health volunteers as health-control group. The peripheral T-cell subgroups and the expression of CD28, ICOS, CD152 and PD-1 in health-control volunteers and disease-control patients were analyzed. In Tac group, the same analysis was performed at second week, first month, second month and third month after transplantation. Results There was no significant difference in CD3^ ＋ T lymphocytes among hepatic-disease-control group, health control group and Tac group at all time points （P〉0. 05）. As Tac-treatment went on, the expression of CD4^＋ T lymphocytes was decreased gradually, and significantly lower than in health-control group at 3rd month after transplantation （P〈0. 05） ; the expression of CD8^＋ T lymphocytes was increased gradually back to the health level. In FK506-treated group, the expression of ICOS in T lymphocytes remained much lower than the health control group （P〈0. 05） ; the expression of CD28 in CD4^＋ T lymphocytes went back to the health level （P〈0. 05）, and that on the surface of CD8^＋ T lymphocytes remained at low level （P〈0. 05） ; at the same time,the expression of CD152 and PD-1 was always significantly higher than in the healthcontrol group （P〈0. 05）. Conclusion In allo-liver recipients receiving immuno-suppressive treatment mainly based on Tac, the disturhance of T lymphocyte subgroups were corrected, the expression of CD28 and ICOS on them was down-regulated while the expression of CD152 and PD-1 up-regulated, and the transplant rejection was inhibited through the regulation of co-stimulatory signal.