The University of Southampton
University of Southampton Institutional Repository

Natural killer cell maturation markers in the human liver and expansion of an NKG2C+KIR+ population

Natural killer cell maturation markers in the human liver and expansion of an NKG2C+KIR+ population
Natural killer cell maturation markers in the human liver and expansion of an NKG2C+KIR+ population
Background: selected populations of murine natural killer (NK) cells possess memory features to haptens, cytokines, and viruses. Liver-specific adhesion molecules CXCR6 and CD49a have been identified as surface markers in mice. In people, expansion of long-lived terminally differentiated NKG2C+ populations occur in the blood after viral infection. We aimed to compare intrahepatic and blood NK cell receptor expression to determine the existence of CD49a+ and CXCR6+ NK cells in human liver and define the maturation status of NKG2C+ NK cells at this site.

Methods: tissue samples were taken from the liver margin of 39 patients with hepatic metastases and flushed with chelating buffer followed by collagenase or mechanical digestion. Paired peripheral blood samples were taken from 15 patients, the remainder being unpaired. Mononuclear cells were isolated by ficoll separation and cell surface staining performed for CD3, CD56, CD16, CD57, CD117, CD161, CD158a, CD158b, CD49a, CD49b, CXCR6, NKG2C, and NKp46. Statistical analysis to compare intrahepatic and blood NK cell receptor expression included the median, IQR, and Mann-Whitney U test

Findings: frequencies of NK cell precursors were similar in the liver and the blood (0·91% [0·62–3·26] vs 0·87 [0·41–1·52]); however, expression of all later markers of maturity were reduced including CD16 (47% [40·4–61·4] vs 88·7 [82·2–93·2], p<0·0001), CD57 (30·7% [25·0–53·9] vs 73·4 [70·4–87·6], p=0·0003), and KIR (11·2% [7·5–14·5] vs 26·7 [17·3–30·8], p<0·0001). Expanded hepatic CD16– NK cells were particularly immature with reduced CD57 and increased CD161 compared with the blood. NKG2C+ NK cells were found in similar frequencies in liver and blood. The hepatic NKG2C+ population was terminally differentiated, as in the circulation, but demonstrated a three-fold increase in KIR expression compared with NKG2C– counterparts, which was not seen in the blood. As in previously published research in mice, CD49a+ and CXCR6+ NK cells were liver resident (6·5% [3·9–14·6] liver vs 2·1 [1·3–4·3] blood, p<0·0001, and 65·3 [48·1–75·2] vs 4·5 [1·43–12·12], p=0·0039, respectively). Both populations were immature, with reduced KIR expression.

Interpretation: we have shown that the liver contains an expanded population of immature CD16– NK cells. These cells might traffic from the blood and then differentiate into hepatic-specific CD49a+ and CXCR6+ NK cells. The function of these subsets is unknown but their immaturity hints against memory. Terminally differentiated NKG2C+ cells show KIR expansion in the human liver and probably represent an antigen-experienced population, raising the question of whether the liver is a site of NK cell memory acquisition
0140-6736
S45
Hydes, Theresa
d842d1ec-c64a-4934-a5a2-7316fea65767
Abuhilal, Mohammed
0f518131-9660-42b1-9937-c27c0a7d631b
Armstrong, Thomas
3b87df01-cd08-4048-91c4-7390c73a5960
Primrose, John
d85f3b28-24c6-475f-955b-ec457a3f9185
Takhar, Arjun
e2f77012-0993-42e6-af95-597a73b6ce45
Khakoo, Salim
6c16d2f5-ae80-4d9b-9100-6bfb34ad0273
Hydes, Theresa
d842d1ec-c64a-4934-a5a2-7316fea65767
Abuhilal, Mohammed
0f518131-9660-42b1-9937-c27c0a7d631b
Armstrong, Thomas
3b87df01-cd08-4048-91c4-7390c73a5960
Primrose, John
d85f3b28-24c6-475f-955b-ec457a3f9185
Takhar, Arjun
e2f77012-0993-42e6-af95-597a73b6ce45
Khakoo, Salim
6c16d2f5-ae80-4d9b-9100-6bfb34ad0273

Hydes, Theresa, Abuhilal, Mohammed, Armstrong, Thomas, Primrose, John, Takhar, Arjun and Khakoo, Salim (2015) Natural killer cell maturation markers in the human liver and expansion of an NKG2C+KIR+ population. The Lancet, 385, supplement 1, S45. (doi:10.1016/S0140-6736(15)60360-9). (PMID:26312867)

Record type: Article

Abstract

Background: selected populations of murine natural killer (NK) cells possess memory features to haptens, cytokines, and viruses. Liver-specific adhesion molecules CXCR6 and CD49a have been identified as surface markers in mice. In people, expansion of long-lived terminally differentiated NKG2C+ populations occur in the blood after viral infection. We aimed to compare intrahepatic and blood NK cell receptor expression to determine the existence of CD49a+ and CXCR6+ NK cells in human liver and define the maturation status of NKG2C+ NK cells at this site.

Methods: tissue samples were taken from the liver margin of 39 patients with hepatic metastases and flushed with chelating buffer followed by collagenase or mechanical digestion. Paired peripheral blood samples were taken from 15 patients, the remainder being unpaired. Mononuclear cells were isolated by ficoll separation and cell surface staining performed for CD3, CD56, CD16, CD57, CD117, CD161, CD158a, CD158b, CD49a, CD49b, CXCR6, NKG2C, and NKp46. Statistical analysis to compare intrahepatic and blood NK cell receptor expression included the median, IQR, and Mann-Whitney U test

Findings: frequencies of NK cell precursors were similar in the liver and the blood (0·91% [0·62–3·26] vs 0·87 [0·41–1·52]); however, expression of all later markers of maturity were reduced including CD16 (47% [40·4–61·4] vs 88·7 [82·2–93·2], p<0·0001), CD57 (30·7% [25·0–53·9] vs 73·4 [70·4–87·6], p=0·0003), and KIR (11·2% [7·5–14·5] vs 26·7 [17·3–30·8], p<0·0001). Expanded hepatic CD16– NK cells were particularly immature with reduced CD57 and increased CD161 compared with the blood. NKG2C+ NK cells were found in similar frequencies in liver and blood. The hepatic NKG2C+ population was terminally differentiated, as in the circulation, but demonstrated a three-fold increase in KIR expression compared with NKG2C– counterparts, which was not seen in the blood. As in previously published research in mice, CD49a+ and CXCR6+ NK cells were liver resident (6·5% [3·9–14·6] liver vs 2·1 [1·3–4·3] blood, p<0·0001, and 65·3 [48·1–75·2] vs 4·5 [1·43–12·12], p=0·0039, respectively). Both populations were immature, with reduced KIR expression.

Interpretation: we have shown that the liver contains an expanded population of immature CD16– NK cells. These cells might traffic from the blood and then differentiate into hepatic-specific CD49a+ and CXCR6+ NK cells. The function of these subsets is unknown but their immaturity hints against memory. Terminally differentiated NKG2C+ cells show KIR expansion in the human liver and probably represent an antigen-experienced population, raising the question of whether the liver is a site of NK cell memory acquisition

Full text not available from this repository.

More information

Published date: 26 February 2015
Organisations: Cancer Sciences, Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 381212
URI: https://eprints.soton.ac.uk/id/eprint/381212
ISSN: 0140-6736
PURE UUID: 26a8b0d4-1155-4c38-bd57-7f2546c0b25b
ORCID for John Primrose: ORCID iD orcid.org/0000-0002-2069-7605

Catalogue record

Date deposited: 25 Sep 2015 13:14
Last modified: 06 Oct 2018 00:39

Export record

Altmetrics

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of https://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×