AI Article Synopsis
- CD161-expressing CD8 T cells include two groups with different T-cell receptor characteristics, and their role in disease progression during chronic hepatitis B infection is not well understood.
- This study analyzed blood from chronic hepatitis B patients and found that CD161CD8 T cells were elevated and hyperactivated, but their increase did not effectively control HBV replication.
- The findings suggest that while these T cells have enhanced antiviral capacity, they exhibit impaired cytokine production and increased inflammatory characteristics, indicating a shift towards a more pathogenic role in liver injury.
Article Abstract
Background & Aims: CD161-expressing CD8 T cells consist of mucosal-associated invariant T cells with semi-invariant T-cell receptor (TCR) use and non-mucosal-associated invariant T CD161CD8 T cells with polyclonal TCR repertoire. Although CD161CD8 T cells are enriched in liver and embrace hepatitis B virus (HBV)-specific T cells in chronic hepatitis B (CHB) patients, their roles in disease progression remain poorly understood. This study aimed to decipher their profiling and dynamic changes during chronic HBV infection.
Methods: Blood samples from 257 CHB patients and nontumor liver specimens from 73 HBV-positive patients were analyzed for CD161CD8 T-cell characterization by flow cytometry, TCR repertoire determination, transcriptomic analyses, and cell experiments.
Results: CD161CD8 T cells were increased and hyperactivated in patients, while positive correlation between the CD161CD8 T-cell ratio and HBV-DNA level suggested this was insufficient to control HBV replication. The overlap of complementarity determining region 3 sequences supported the switch between CD161CD8 and CD161CD8 populations. Although CD161CD8 T cells were endowed with innateness phenotype and enhanced antiviral capacity, the population from patients had impaired type I cytokine production, and increased interleukin 17 and granzyme B secretion. The increased CD161CD8 T cells and their increased granzyme B secretion correlated positively with inflammation-associated liver injury. Hepatic CD161CD8 T cells showed neutrophil-related pathogenic potential because they had increased transcript signatures and proinflammatory cytokine production in neutrophil recruitment- and response-related pathways that changed consistently in the injured liver.
Conclusions: Our results highlight the reduced antiviral potency but increased pathogenic potential of CD161CD8 T cells in CHB patients, supporting CD161 expression as a marker of pathogenic CD8 T subset and the intervention target for liver injury.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10060787 | PMC |
| http://dx.doi.org/10.1016/j.jcmgh.2023.02.001 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Cytotoxic CD161CD8 T cells contribute to the pathogenesis of systemic lupus erythematosus.
EBioMedicine
April 2023
Translational Medical Center for Stem Cell Therapy, Institute for Regenerative Medicine, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, 200127, China; Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China. Electronic address:
Background: Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease affecting multiple organs and tissues with high cellular heterogeneity. CD8 T cell activity is involved in the SLE pathogenesis. However, the cellular heterogeneity and the underlying mechanisms of CD8 T cells in SLE remain to be identified.
View Article and Find Full Text PDFIncreased Non-MAIT CD161CD8 T Cells Display Pathogenic Potential in Chronic HBV Infection.
Cell Mol Gastroenterol Hepatol
April 2023
Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:
Article Synopsis
- CD161-expressing CD8 T cells include two groups with different T-cell receptor characteristics, and their role in disease progression during chronic hepatitis B infection is not well understood.
- This study analyzed blood from chronic hepatitis B patients and found that CD161CD8 T cells were elevated and hyperactivated, but their increase did not effectively control HBV replication.
- The findings suggest that while these T cells have enhanced antiviral capacity, they exhibit impaired cytokine production and increased inflammatory characteristics, indicating a shift towards a more pathogenic role in liver injury.
Association Between Impaired Vα7.2+CD161++CD8+ (MAIT) and Vα7.2+CD161-CD8+ T-Cell Populations and Gut Dysbiosis in Chronically HIV- and/or HCV-Infected Patients.
Front Microbiol
August 2019
Department of Health Sciences, Clinic of Infectious Diseases, ASST Santi Paolo e Carlo, University of Milan, Milan, Italy.
Both HIV and HCV infections feature increased microbial translocation (MT) and gut dysbiosis that affect immune homeostasis and disease outcome. Given their commitment to antimicrobial mucosal immunity, we investigated mucosal-associated invariant T (MAIT) cells and Vα7.2+CD161- T-cell frequency/function and their possible associations with MT and gut dysbiosis, in chronic HIV and/or HCV infections.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!