CAJ | 학술논문

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、CD152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>0.05).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Tac 3个月时,明显低于正常对照组(P<0.05);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<0.05).同时,Tac组T淋巴细胞亚群表面CD152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.
목적 관찰사용타극막사(Tac)적간이식수자외주혈중T림파세포아군급CD28가족공자격분자표체적변화급기의의.방법 이접수동충이체간이식적수자20례위Tac조,술후채용Tac、매분산지(혹류서표령)화당피질격소예방배척반응;이등대간이식적종말기간장질병환자20례위간병대조조;이건강지원자20명위정상대조조.측정정상대조조지원자화간병대조조환자적외주혈중T림파세포아군급기CD28、가유도공자격분자(ICOS)、CD152화정서성사망인자1(PD-1)적표체;분별측정Tac조사용Tac후2주、1개월、2개월화3개월시외주혈중T림파세포아군급기CD28、ICOS、CD152화PD-1적표체.결과 간병대조조、정상대조조화Tac조각시점간적CD3+ T림파세포적차이무통계학의의(P>0.05).수착사용Tac시간적연장,Tac조CD4+ T림파세포지속하강,지사용Tac 3개월시,명현저우정상대조조(P<0.05);CD8+ T림파세포축점증가지정상수평.Tac조T림파세포아군표면ICOS분자표체지속저우정상대조조(P<0.05),CD4+ T림파세포표면CD28분자표체회복지정상수평(P>0.05),이CD8+ T림파세포표면CD28분자지속저표체(P<0.05).동시,Tac조T림파세포아군표면CD152분자화PD-1분자적표체균지속고우정상대조조(P<0.05).결론 간이식환자접수이Tac위주적면역억제치료,기T림파세포아군평형문란득도규정,T림파세포아군표면CD28분자화ICOS분자적표체하조,CD152분자화PD-1분자적표체상조,통과공자격신호적조절래체도억제배척반응적목적.
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+ Tlymphocytes 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 hack 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 healthlevel (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 health-control group (P<0.05). Conclusion In allo-liver recipients receiving immuno-suppressive treatment mainly based on Tac, the disturbance 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.