Innate-like bystander-activated CD38+HLA-DR+CD8+T cells play a pathogenic role in patients with chronic hepatitis C

Chien Hao Huang, Jian He Fan, Wen Juei Jeng, Shu Ting Chang, Chan-Keng Yang, Wei Teng, Tsung Han Wu, Yi Chung Hsieh, Wei Ting Chen, Yi Cheng Chen, I-Shyan Sheen, Yung-Chang Lin*, Chun Yen Lin*

*此作品的通信作者

研究成果: 期刊稿件文章同行評審

11 引文 斯高帕斯(Scopus)

摘要

Background and Aims: HCV-specific T cells are few and exhausted in patients with chronic hepatitis C (CHC). Whether these T cells are responsible for the liver damage and fibrosis is still debated. However, cluster of differentiation 38–positive (CD38+) human leukocyte antigen DR–positive (HLA-DR+) CD8+ T cells are regarded as bystander CD8+ T cells that cause liver injury in acute hepatitis. We propose that these innate CD8+ T cells play a pathogenic role in CHC. Methods: Lymphocytes from peripheral blood were obtained from 108 patients with CHC and 43 healthy subjects. Immunophenotyping, functional assays, T-cell receptor (TCR) repertoire, and cytotoxic assay of CD38+HLA-DR+CD8+ T cells were studied. Results: The percentage of CD38+HLA-DR+CD8+ T cells increased significantly in patients with CHC. These cells expressed higher levels of effector memory and proinflammatory chemokine molecules and showed higher interferon-γ production than CD38HLA-DR CD8 T cells. They were largely composed of non-HCV-specific CD8+ T cells as assessed by HLA-A2-restricted pentamers and next-generation sequencing analysis of the TCR repertoire. In addition, these CD38+HLA-DR+CD8+ T cells had strong cytotoxicity, which could be inhibited by anti–DNAX accessory molecule 1, anti–NKG2 family member D, and anti–natural killer NKp30 antibodies. Lastly, the percentage of CD38+HLA-DR+CD8+ T cells was significantly associated with liver injury and fibrosis and decreased significantly along with serum alanine aminotransferase normalization after successful direct-acting antiviral treatment. Conclusions: The TCR-independent, cytokine-responsive bystander CD38+HLA-DR+CD8+ T cells are strongly cytotoxic and play a pathogenic role in patients with CHC.

原文英語
頁(從 - 到)803-818
頁數16
期刊Hepatology
76
發行號3
DOIs
出版狀態已出版 - 09 2022

文獻附註

Publisher Copyright:
© 2022 American Association for the Study of Liver Diseases.

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