IL-15-induced CD38HLA-DRCD8 T cells Correlate with Liver Injury Via NKG2D in Chronic Hepatitis B Cirrhosis

Overview

Journal Clin Transl Immunology

Specialty Allergy & Immunology

Date 2024 Oct 17

PMID 39416768

Authors

Jing Fan

Min Xu

Ke Liu

Wanping Yan

Huanyu Wu

Hongliang Dong

Yongfeng Yang

Wei Ye

Affiliations

Soon will be listed here.

Abstract

Objectives: CD8 T cells play a critical role in the immune dysfunction associated with liver cirrhosis. CD38HLA-DRCD8 T cells, or bystander-activated CD8 T cells, are involved in tissue injury but their specific contribution to liver cirrhosis remains unclear. This study sought to identify the mechanism for CD38HLA-DRCD8 T cell-mediated pathogenesis during liver cirrhosis.

Methods: The immunophenotype, antigen specificity, cytokine secretion and cytotoxicity-related indicators of CD38HLA-DRCD8 T cells were determined using flow cytometry. The functional properties of these cells were assessed using transcriptome analysis. CD38HLA-DRCD8 T-cell killing was detected using cytotoxicity and antibody-blocking assays.

Results: The proportion of CD38HLA-DRCD8 T cells was significantly elevated in liver cirrhosis patients and correlated with tissue damage. Transcriptome analysis revealed that these cells had innate-like functional characteristics. This CD8 T-cell population primarily consisted of effector memory T cells and produced a high level of cytotoxicity-related cytokines, granzyme B and perforin. IL-15 promoted CD38HLA-DRCD8 T-cell activation and proliferation, inducing significant TCR-independent cytotoxicity mediated through NKG2D.

Conclusions: CD38HLA-DRCD8 T cells correlated with cirrhosis-related liver injury and contributed to liver damage by signalling through NKG2D in a TCR-independent manner.

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