Hepatitis B Virus-Specific CD8+ T Cells Maintain Functional Exhaustion after Antigen Reexposure in an Acute Activation Immune Environment.
Hepatitis B Virus-Specific CD8+ T Cells Maintain Functional Exhaustion after Antigen Reexposure in an Acute Activation Immune Environment.
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乙型肝炎病毒特异性 CD8 T 细胞在急性激活免疫环境中再次暴露抗原后维持功能衰竭
DOI：
10.3389/fimmu.2018.00219
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发表时间：
2018
影响因子：
7.3
通讯作者：
Liu J
中科院分区：
文献类型：
--
作者：
Wang Q;Pan W;Liu Y;Luo J;Zhu D;Lu Y;Feng X;Yang X;Dittmer U;Lu M;Yang D;Liu J
慢性乙型肝炎病毒(HBV)感染的特征是存在功能耗竭的HBV特异性CD8+T细胞。为了表征这些细胞可能的残留效应能力，我们在急性激活免疫环境中将慢性复制的乙肝病毒小鼠的CD8+T细胞重新暴露于乙肝病毒抗原。我们发现，在转移到幼鼠体内后，耗尽的CD8+T细胞对急性乙肝病毒感染的反应与初治的CD8+T细胞的再扩增幅度相当，但其增殖强度明显低于急性乙肝病毒复制小鼠(AR鼠)的CD8+T细胞。供者衰竭的CD8+T细胞和初治的CD8+T细胞在急性乙肝病毒复制作用下的分化表型相似，但与AR小鼠的相应细胞不同。然而，在急性激活免疫环境中，在乙肝病毒再次暴露后，耗尽的CD8+T细胞保持了较少的激活表型，缺乏效应细胞因子的产生和抗病毒功能。因此，我们得出结论，在慢性复制过程中，耗尽的CD8+T细胞经历了一种稳定的功能分化形式，仅靠切换免疫环境不足以实现这些细胞的抗病毒功能重建。
Chronic hepatitis B virus (HBV) infection is characterized by the presence of functionally exhausted HBV-specific CD8+ T cells. To characterize the possible residual effector ability of these cells, we reexposed CD8+ T cells from chronically HBV replicating mice to HBV antigens in an acute activation immune environment. We found that after transfer into naive mice, exhausted CD8+ T cells reexpanded in a comparable magnitude as naive CD8+ T cells in response to acute HBV infection; however, their proliferation intensity was significantly lower than that of CD8+ T cells from acute-resolving HBV replicating mice (AR mice). The differentiation phenotypes driven by acute HBV replication of donor exhausted and naive CD8+ T cells were similar, but were different from those of their counterparts from AR mice. Nevertheless, exhausted CD8+ T cells maintained less activated phenotype, an absence of effector cytokine production and poor antiviral function after HBV reexposure in an acute activation immune environment. We thus conclude that exhausted CD8+ T cells undergo a stable form of dysfunctional differentiation during chronic HBV replication and switching immune environment alone is not sufficient for the antiviral functional reconstitution of these cells.
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