Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea.
Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea; Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
J Hepatol. 2022 Oct;77(4):1059-1070. doi: 10.1016/j.jhep.2022.05.020. Epub 2022 May 27.
BACKGROUND & AIMS: The liver provides a unique niche of lymphocytes enriched with a large proportion of innate-like T cells. However, the heterogeneity and functional characteristics of the hepatic T-cell population remain to be fully elucidated.
We obtained liver sinusoidal mononuclear cells from the liver perfusate of healthy donors and recipients with HBV-associated chronic liver disease (CLD) during liver transplantation. We performed a CITE-seq analysis of liver sinusoidal CD45 cells in combination with T cell receptor (TCR)-seq and flow cytometry to examine the phenotypes and functions of liver sinusoidal CD8 T cells.
We identified a distinct CD56CD161CD8 T-cell population characterized by natural killer (NK)-related gene expression and a uniquely restricted TCR repertoire. The frequency of these cells among the liver sinusoidal CD8 T-cell population was significantly increased in patients with HBV-associated CLD. Although CD56CD161CD8 T cells exhibit weak responsiveness to TCR stimulation, CD56CD161CD8 T cells highly expressed various NK receptors, including CD94, killer immunoglobulin-like receptors, and NKG2C, and exerted NKG2C-mediated NK-like effector functions even in the absence of TCR stimulation. In addition, CD56CD161CD8 T cells highly respond to innate cytokines, such as IL-12/18 and IL-15, in the absence of TCR stimulation. We validated the results from liver sinusoidal CD8 T cells using intrahepatic CD8 T cells obtained from liver tissues.
In summary, the current study found a distinct CD56CD161CD8 T-cell population characterized by NK-like activation via TCR-independent NKG2C ligation. Further studies are required to elucidate the roles of liver sinusoidal CD56CD161CD8 T cells in immune responses to microbial pathogens or liver immunopathology.
The role of different immune cell populations in the liver is becoming an area of increasing interest. Herein, we identified a distinct T-cell population that had features similar to those of natural killer (NK) cells - a type of innate immune cell. This distinct population was expanded in the livers of patients with chronic liver disease and could thus have pathogenic relevance.
肝脏为富含大量固有样 T 细胞的淋巴细胞提供了独特的生态位。然而，肝 T 细胞群体的异质性和功能特征仍有待充分阐明。
我们从健康供体和肝移植期间 HBV 相关慢性肝病（CLD）患者的肝灌流液中获得肝窦单核细胞。我们对肝窦 CD45 细胞进行 CITE-seq 分析，结合 T 细胞受体（TCR）-seq 和流式细胞术，以检查肝窦 CD8 T 细胞的表型和功能。
我们鉴定了一种独特的 CD56CD161CD8 T 细胞群，其特征在于 NK 相关基因表达和独特受限的 TCR 库。在 HBV 相关 CLD 患者中，这群细胞在肝窦 CD8 T 细胞群体中的频率显著增加。尽管 CD56CD161CD8 T 细胞对 TCR 刺激的反应较弱，但 CD56CD161CD8 T 细胞高度表达各种 NK 受体，包括 CD94、杀伤免疫球蛋白样受体和 NKG2C，并在缺乏 TCR 刺激的情况下发挥 NKG2C 介导的 NK 样效应功能。此外，CD56CD161CD8 T 细胞在缺乏 TCR 刺激的情况下，对先天细胞因子（如 IL-12/18 和 IL-15）高度反应。我们使用从肝组织中获得的肝内 CD8 T 细胞验证了肝窦 CD8 T 细胞的结果。
总之，本研究发现了一种独特的 CD56CD161CD8 T 细胞群，其特征是通过 TCR 非依赖性 NKG2C 连接进行 NK 样激活。需要进一步的研究来阐明肝窦 CD56CD161CD8 T 细胞在对微生物病原体或肝免疫病理学的免疫反应中的作用。
不同免疫细胞群体在肝脏中的作用正成为一个日益受到关注的领域。在此，我们鉴定了一种独特的 T 细胞群，其具有类似于自然杀伤（NK）细胞的特征 - 一种先天免疫细胞。该独特群体在慢性肝病患者的肝脏中扩增，因此可能具有致病性。
