德国弗莱堡大学Maike Hofmann等研究人员合作发现，效应T细胞的减弱与慢性HBV感染的控制有关。2024年8月28日，《自然—免疫学》杂志在线发表了这项成果。

研究人员表示，乙型肝炎病毒（HBV）特异性CD8⁺ T细胞在急性自限性HBV感染中起主导作用，但在慢性HBV感染中功能受损。这些功能缺陷与代谢和表型异质性有关，但不同亚群的HBV特异性CD8⁺ T细胞在多大程度上仍能抑制病毒复制尚不明确。

研究人员通过深度分析、功能测试和慢性HBV感染不同阶段的HBV特异性CD8⁺ T细胞干扰研究，探讨了这一问题。数据揭示了一种效应CD8⁺ T细胞减弱的机制，这种机制与经典的CD8⁺ T细胞耗竭同时出现。减弱的HBV特异性CD8⁺ T细胞具有细胞毒性特征，并表现出由抗原识别和TGFβ信号调控的减弱的效应分化程序，并与慢性HBV感染期间的病毒控制相关联。这些发现确定了一个与免疫效力相关的CD8⁺ T细胞特定亚群，并具有免疫治疗潜力。

附：英文原文

Title: Attenuated effector T cells are linked to control of chronic HBV infection

Author: Heim, Kathrin, Sagar, Sogukpinar, zlem, Llewellyn-Lacey, Sian, Price, David A., Emmerich, Florian, Kraft, Anke R. M., Cornberg, Markus, Kielbassa, Sophie, Knolle, Percy, Wohlleber, Dirk, Bengsch, Bertram, Boettler, Tobias, Neumann-Haefelin, Christoph, Thimme, Robert, Hofmann, Maike

Issue&Volume: 2024-08-28

Abstract: Hepatitis B virus (HBV)-specific CD8+T cells play a dominant role during acute-resolving HBV infection but are functionally impaired during chronic HBV infection in humans. These functional deficits have been linked with metabolic and phenotypic heterogeneity, but it has remained unclear to what extent different subsets of HBV-specific CD8+T cells still suppress viral replication. We addressed this issue by deep profiling, functional testing and perturbation of HBV-specific CD8+T cells during different phases of chronic HBV infection. Our data revealed a mechanism of effector CD8+T cell attenuation that emerges alongside classical CD8+T cell exhaustion. Attenuated HBV-specific CD8+T cells were characterized by cytotoxic properties and a dampened effector differentiation program, determined by antigen recognition and TGFβ signaling, and were associated with viral control during chronic HBV infection. These observations identify a distinct subset of CD8+T cells linked with immune efficacy in the context of a chronic human viral infection with immunotherapeutic potential.

DOI: 10.1038/s41590-024-01928-4

Source: https://www.nature.com/articles/s41590-024-01928-4