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Gut. 2018 Nov 28. pii: gutjnl-2018-317071. doi: 10.1136/gutjnl-2018-317071. [Epub ahead of print]
Fine needle aspirates comprehensively sample intrahepatic immunity.
Gill US#1, Pallett LJ#2, Thomas N2, Burton AR2, Patel AA3, Yona S3, Kennedy PTF#1, Maini MK#2.
Author information
1
Barts Liver Centre, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
2
Division of Infection and Immunity, Institute of Immunity and Transplantation, University College London, London, UK.
3
Division of Medicine, University College London, London, UK.
#
Contributed equally
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)hiCD39hi tissue-resident memory CD8 T cells (CD69+CD103+) and liver-resident NK cells (CXCR6+T-betloEomeshi), 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.
© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY. Published by BMJ.
KEYWORDS:
HBV-specific T cells; fine needle aspirate; hepatitis B virus; hepatocytes; intrahepatic-immune monitoring; liver biopsy; tissue-resident immunity
PMID:
30487267
DOI:
10.1136/gutjnl-2018-317071 |
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