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Cited by 87Hepatitis B Virus StudiesLiver physiology and pathologyHepatitis C virus research

Fine needle aspirates comprehensively sample intrahepatic immunity

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Gill, Upkar S, Pallett, Laura J, Thomas, Niclas, Burton, Alice R, Patel, Amit A, Yona, Simon, Kennedy, Patrick T F, Maini, Mala K·2019·Gut
DOI 10.1136/gutjnl-2018-317071PMC PMC6691856
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Abstract

Objective In order to refine new therapeutic strategies in the pipeline for HBV cure, evaluation of virological and immunological changes compartmentalised at the site of infection will be required. We therefore investigated if liver fine needle aspirates (FNAs) could comprehensively sample the local immune landscape in parallel with viable hepatocytes. Design Matched blood, liver biopsy and FNAs from 28 patients with HBV and 15 without viral infection were analysed using 16-colour multiparameter flow cytometry. Results The proportion of CD4 T, CD8 T, Mucosal Associated Invariant T cell (MAIT), Natural Killer (NK) and B cells identified by FNA correlated with that in liver biopsies from the same donors. Populations of Programmed Death-1 (PD-1) hi CD39 hi tissue-resident memory CD8 T cells (CD69 + CD103 + ) and liver-resident NK cells (CXCR6 + T-bet lo Eomes hi ), were identified by both FNA and liver biopsy, and not seen in the blood. Crucially, HBV-specific T cells could be identified by FNAs at similar frequencies to biopsies and enriched compared with blood. FNAs could simultaneously identify populations of myeloid cells and live hepatocytes expressing albumin, Scavenger Receptor class B type 1 (SR-B1), Programmed Death-Ligand 1 (PD-L1), whereas hepatocytes were poorly viable after the processing required for liver biopsies. Conclusion We demonstrate for the first time that FNAs identify a range of intrahepatic immune cells including locally resident sentinel HBV-specific T cells and NK cells, together with PD-L1-expressing hepatocytes. In addition, we provide a scoring tool to estimate the extent to which an individual FNA has reliably sampled intrahepatic populations rather than contaminating blood. The broad profiling achieved by this less invasive, rapid technique makes it suitable for longitudinal monitoring of the liver to optimise new therapies for HBV.

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  • Their constant presence within the liver is not mere confinement; it is a strategic placement, ensuring they are the frontline defence against pathogens and tissue damage.

    “Their constant presence within the liver is not mere confinement; it is a strategic placement, ensuring they are the frontline defence against pathogens and tissue damage(108-110).”

    From The liver as a central "hub" of the immune system: pathophysiological implications (2025) · cites this paper as [110]

    The Introduction describes liver-resident immune cells as providing front-line immunosurveillance and rapid antiviral defence, and the Discussion calls resident T and NK cells front-line defenders against HBV. Neither passage says their residence is a strategic placement that protects against tissue damage; the paper's defence claim is narrower. (LLM, conf=0.86)

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Sorted by citations

Authors
Gill, U. S., Pallett, L. J., Thomas, N., Burton, A. R., Patel, A. A., Yona, S., Kennedy, P. T. F., & Maini, M. K.
Affiliations
  • Queen Mary University of London (GB)
  • University College London (GB)
Corresponding author
Maini, Mala K
ORCID
Venue
Gut
Publisher
BMJ
Published
2018-11-28
Volume
68
Issue
8
Pages
1493-1503
ISSN
  • 0017-5749 (ISSN-L)
  • 1468-3288
DOI
10.1136/gutjnl-2018-317071
PMC
PMC6691856
OpenAlex
W2902075768
Cited by
87
References
6
Citations by year
2026: 2 · 2025: 15 · 2024: 6 · 2023: 15 · 2022: 21 · 2021: 12 · 2020: 11 · 2019: 5
FWCI
5.47
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Gut (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • HighWire Press Open Archive (submittedVersion)
  • Queen Mary Research Online (Queen Mary University of London) (submittedVersion, cc-by)
Funders
  • Medical Research Council
  • Programme Grants for Applied Research
  • Barts and The London School of Medicine and Dentistry
  • Wellcome Trust
Topics
  • Health Sciences › Medicine › Epidemiology › Hepatitis B Virus Studies
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Health Sciences › Medicine › Hepatology › Hepatitis C virus research
Keywords
hepatitis B virus, HBV-specific T cells, PD-1, PD-L1, hepatocyte viability, mucosal-associated invariant T cells, liver biopsy comparison, HBV cure
MeSH terms
Adult, Algorithms, B-Lymphocytes, DNA, Viral, Female, Flow Cytometry, Hepatitis B virus, Humans, Killer Cells, Natural, Male, Reproducibility of Results, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Hepatitis B, Chronic, Hepatocytes, Biopsy, Fine-Needle, Scavenger Receptors, Class B, Programmed Cell Death 1 Receptor

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