程序性死亡因子1高表达影响急性乙型肝炎患者体内乙肝病毒特异性CD8^＋T细胞凋亡的研究  

PD-1 up-regulation influenced apoptosis of HBV-speeific CD8 T cells in patients with acute resolved hepatitis B

作　　者：徐斌[1] 张政 石英[1] 陈新月[1] 王福生 

机构地区：[1]首都医科大学附属北京佑安医院感染科,100069 [2]解放军第三O二医院生物工程室

出　　处：《中华医学杂志》2009年第17期1158-1161,共4页National Medical Journal of China

基　　金：国家自然科学基金（30730088）;国家杰出青年科学基金（30525042）

摘　　要：目的观察急性乙型肝炎发病过程中患者体内病毒特异性CTL细胞上免疫抑制性分子程序性死亡因子1（programmed death1，PD-1）的表达与凋亡的关系。方法针对HBV不同表位合成2种pentamer，同时针对CMV表位合成pentamer作为对照。采集15例HLA-A2阳性的急性乙型肝炎患者（AHB）的外周血，流式细胞仪分析各病毒特异性CTL细胞表面PD-1分子表达水平及其凋亡水平；同时进行体外实验验证PD-1表达与凋亡的关系。结果AHB患者发病早期HBV特异性的CD8^＋T细胞表面PD-1表达水平明显增高，增高的PD-1水平与HBV特异性CD8^＋T细胞自发凋亡呈明显正相关；体外共培养HepG2．215细胞与AHB患者CD8^＋T细胞，可明显诱导CD8^＋T细胞凋亡。结论在HBV急性感染早期，HBV特异性CD8^＋T细胞PD-1表达明显升高，并明显诱导了病毒特异性CD8^＋T凋亡，从而避免了AHB患者肝脏遭受更为严重的免疫损伤。Objective Programmed death-1 （PD-1） up-regulation can impair virus-specific CD8 ^＋T-cell responses during chronic viral infection. Whether PD-1 affects virus-specific CD8 T cells in humans with acute hepatitis B virus （HBV） infection remains unknown. This study aimed to characterize the PD-1 expression during acute hepatitis B （ AHB ）, and further addressed how PD-1 regulates the apoptosis of CD8^＋ T cells in this disease. Methods PD-1 expression on HBV env-183-191-, env-335-343- and CMV pp65-specific CD8^＋ T cells were quantitatively analyzed by flow cytometry in peripheral blood from 15 HLA- A2-positive AHB patients. The spontaneous apoptosis indicated by annexin V expression was performed for analyses of the impact of PD-1 expression. We also confirmed the effects of PD-1/PD-L1 pathway on the in vitro apoptosis of CD8^＋ T cells through PD-1 blockade assay. Results PD-1 expression on HBV-specific CD8^＋ T cells was significantly up-regulated compared with CMV-speeifie CD8^＋ T cells in the early phase of acute HBV infection. High levels of PD-1 expression significantly correlated with the apoptosis of HBV- specific CD8^＋ T cells. Blockade of PD-1 ligation using anti-PD-L1 rescued the HepG2. 215-induced CD8^ ＋ T cell apoptosis. Condusion PD-1/PD-L1 inhibitory pathway is actively involved in the apoptotic regulation of HBV-speeifie CD8 ^＋ T cells at early phase of acute HBV infection, and high PD-1 expression by HBV- specific CD8^＋ T cells appear to efficiently temper liver damage.

关 键 词：肝炎 乙型 T淋巴细胞 细胞毒性 免疫抑制 

分 类 号：R686[医药卫生—骨科学]