Department of Infectious Diseases, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
World J Gastroenterol. 2010 Feb 7;16(5):618-24. doi: 10.3748/wjg.v16.i5.618.
To investigate if and how programmed death type-1 (PD-1) expression affects the natural course of hepatitis B virus (HBV) infection.
Sixty-four patients in different natural stages of chronic HBV infection were enrolled in this study. PD-1 expression in total T cells was detected by flow cytometry. Levels of total CD8+ T cell responses and proliferation in relation to PD-1 expression levels were analyzed with intracellular staining and PD-1/PD-L1 blockage.
The PD-1 expression in T cells was dynamically changed during the natural course of chronic HBV infection, did not significantly increase in the immune tolerance phase, and returned to normal in the inactive virus carrier stage. Blockage of the PD-1/PD-L1 pathway could not affect the T-cell response in the immune tolerance and inactive virus carrier stages of chronic HBV infection. However, it could significantly restore the T-cell response in the immune clearance stage of chronic HBV infection. Furthermore, the PD-1 expression level in T cells was associated with the alanine aminotransferase level during the immune clearance stage of chronic HBV infection.
The PD-l/PD-L1 pathway plays a different role in T-cell response during the natural course of chronic HBV infection.
研究程序性死亡受体 1(PD-1)的表达是否及如何影响乙型肝炎病毒(HBV)感染的自然病程。
本研究纳入了处于慢性 HBV 感染不同自然阶段的 64 例患者。采用流式细胞术检测总 T 细胞中的 PD-1 表达。通过细胞内染色和 PD-1/PD-L1 阻断分析,分析 PD-1 表达水平与总 CD8+T 细胞应答和增殖的关系。
T 细胞中的 PD-1 表达在慢性 HBV 感染的自然病程中发生动态变化,在免疫耐受期无显著增加,并在非活动病毒携带期恢复正常。PD-1/PD-L1 通路阻断不能影响慢性 HBV 感染免疫耐受和非活动病毒携带期的 T 细胞反应。然而,它可以显著恢复慢性 HBV 感染免疫清除期的 T 细胞反应。此外,T 细胞中的 PD-1 表达水平与慢性 HBV 感染免疫清除期的丙氨酸氨基转移酶水平相关。
PD-1/PD-L1 通路在慢性 HBV 感染的自然病程中对 T 细胞反应发挥不同的作用。