乙型肝炎病毒特异性CD8 + T细胞在急性激活免疫环境中重新暴

StephenW

Front Immunol. 2018 Feb 12;9:219. doi: 10.3389/fimmu.2018.00219. eCollection  2018.
Hepatitis B Virus-Specific CD8+ T Cells Maintain Functional Exhaustion after Antigen Reexposure in an Acute Activation Immune Environment.Wang Q1,2, Pan W1, Liu Y1, Luo J1, Zhu D1, Lu Y2, Feng X2, Yang X2, Dittmer U3, Lu M3, Yang D1,2, Liu J1,2.
Author information
1Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.2Institute of Infection and Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.3Institute for Virology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany.

AbstractChronic 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.


KEYWORDS: CD8+ T cell; cell transfer; functional exhaustion; hepatitis B virus; immune environment

PMID:29483916PMCID:PMC5816053DOI:10.3389/fimmu.2018.00219

StephenW

Front Immunol。 2018年2月12日; 9：219。 doi：10.3389 / fimmu.2018.00219。 eCollection 2018年。
乙型肝炎病毒特异性CD8 + T细胞在急性激活免疫环境中重新暴露抗原后维持功能衰竭。
Wang Q1,2，Pan W1，Liu Y1，Luo J1，Zhu D1，Lu Y2，Feng X2，Yang X2，Dittmer U3，Lu M3，Yang D1,2，Liu J1,2。
作者信息

1
    华中科技大学同济医学院协和医院感染科，武汉，中国。
2
    华中科技大学同济医学院协和医院感染与免疫研究所，武汉，中国。
3
    埃森大学医院病毒学研究所，德国埃森杜伊斯堡埃森大学。

抽象

慢性乙型肝炎病毒（HBV）感染的特征在于存在功能性耗竭的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HBV复制小鼠的CD8 + T细胞重新暴露于HBV抗原。我们发现在转移到幼稚小鼠体内后，用尽急性CD8 + T细胞重新扩增的数量与原始CD8 + T细胞相当，以回应急性HBV感染;然而，它们的增殖强度显着低于急性解决HBV复制小鼠（AR小鼠）的CD8 + T细胞的增殖强度。急性HBV复制驱动的供体衰竭和初始CD8 + T细胞的分化表型是相似的，但是与AR小鼠的对应物不同。尽管如此，在急性激活免疫环境中HBV再暴露后，耗竭的CD8 + T细胞维持较少的活化表型，不存在效应细胞因子产生和较差的抗病毒功能。因此，我们得出结论：耗尽的CD8 + T细胞在慢性HBV复制期间经历了稳定形式的功能失调分化，并且单独切换免疫环境不足以用于这些细胞的抗病毒功能重构。
关键词：

CD8 + T细胞;细胞转移;功能衰竭;乙型肝炎病毒;免疫环境

结论：
    29483916
PMCID：
    PMC5816053
DOI：
    10.3389 / fimmu.2018.00219