摘要
目的观察急性自限性乙型肝炎发病过程中患者体内病毒抗原特异性细胞毒性T淋巴细胞（CTL）上程序性细胞死亡受体1（PD—1）表达的动态变化特点及其与记忆性抗原特异性CD8’T淋巴细胞形成的关系。方法针对不同表位合成4种五聚体，长期随访收集11例人类白细胞抗原（HLA）-A2阳性的急性乙型肝炎患者的外周血，流式细胞仪检测病毒特异性CTL上免疫抑制性分子PD-1、记忆性分子（CCR7、CD45RA、CD127）和活化标志物CD38的表达情况，并分析其相关性。同时进行肝功能、HBsAg、抗HBs和血清HBVDNA载量检测。结果所有急性自限性乙型肝炎患者发病早期均表现出高频度、病毒抗原多表位的特异性CTL反应，而晚期各表位CTL频率均明显下降。CTL上PD-1表达在早期明显上调；与早期比较，晚期PD-1分子的表达明显降低（t=4．314，P〈0．01）。同时CTL高表达记忆性分子CCR7、CD45RA和CD127，而低表达活化标志物CD38。提永病毒清除后记忆性CD8T淋巴细胞形成。结论在急性自限性乙型肝炎发病过程中，HBV特异性CTL上PD1分子表达的动态变化与记忆性T淋巴细胞的形成密切相关。
Objectives Programmed death-1 （PD-1） up-regulation impairs virus-specific CD8＋ T- cell responses during chronic viral infection. Whether PD-1 expression influences the virus-specific CD8＋ T cells in humans with acute viral infection remains largely undefined. This study aims to characterize the PD- 1 expression during acute hepatitis B （AHB）, and further addresses the association between the PD-1 dynamics and memory T-cell formation during acute HBV infection. Methods Peripheral HBV-specific CD8＋ T cells from 11 HLA-A2-positive AHB patients were longitudinally quantitatively analyzed, and PD-1, memory markers CCR7, CD45RA and CD127 and activation marker CD38 on HBV-specific CD8＋ T ceils were measured using flow cytometric assay. Serum ALT, HBsAg, HBsAb and HBV-DNA levels were evaluated for each subject. Results All 11 AHB patients examined had multiple pentamer-positive CD8＋ T-cell responses in their early phase of HBV infection. Specifically, their PD-1 on pentamer-positive CD8＋ T-cells was significantly up-regulated at the onset of their disease. Following their disease resolution, the dynamic decrease in PD-1 expression was found to correlate with the phenotypic development of memory CD8＋ T cells, indicated by the increases in CCR7, CD45RA and CD127 and decrease in CD38. Conclusion PD-1-mediated negative signaling may be closely associated with memory T-cell formation during acute self-limited hepatitis B.
出处
《中华肝脏病杂志》
CAS
CSCD
北大核心
2008年第9期649-653,共5页
Chinese Journal of Hepatology
基金
国家自然科学基金（30730088）
