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T Cells Infiltrating Diseased Liver Express Ligands for the NKG2D Stress Surveillance System

Huang, W-C; Easom, NJ; Tang, X-Z; Gill, US; Singh, H; Robertson, F; Chang, C; ... Maini, MK; + view all (2017) T Cells Infiltrating Diseased Liver Express Ligands for the NKG2D Stress Surveillance System. Journal of Immunology , 198 (3) pp. 1172-1182. 10.4049/jimmunol.1601313. Green open access

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Abstract

NK cells, which are highly enriched in the liver, are potent regulators of antiviral T cells and immunopathology in persistent viral infection. We investigated the role of the NKG2D axis in T cell/NK cell interactions in hepatitis B. Activated and hepatitis B virus (HBV)–specific T cells, particularly the CD4 fraction, expressed NKG2D ligands (NKG2DL), which were not found on T cells from healthy controls (p < 0.001). NKG2DL-expressing T cells were strikingly enriched within HBV-infected livers compared with the periphery or to healthy livers (p < 0.001). NKG2D+NK cells were also increased and preferentially activated in the HBV-infected liver (p < 0.001), in direct proportion to the percentage of MICA/B-expressing CD4 T cells colocated within freshly isolated liver tissue (p < 0.001). This suggests that NKG2DL induced on T cells within a diseased organ can calibrate NKG2D-dependent activation of local NK cells; furthermore, NKG2D blockade could rescue HBV-specific and MICA/B-expressing T cells from HBV-infected livers. To our knowledge, this is the first ex vivo demonstration that non-virally infected human T cells can express NKG2DL, with implications for stress surveillance by the large number of NKG2D-expressing NK cells sequestered in the liver.

Type: Article
Title: T Cells Infiltrating Diseased Liver Express Ligands for the NKG2D Stress Surveillance System
Open access status: An open access version is available from UCL Discovery
DOI: 10.4049/jimmunol.1601313
Publisher version: http://dx.doi.org/10.4049/jimmunol.1601313
Additional information: This is an open-access article distributed under the terms of the CC-BY 3.0 Unported license.
Keywords: Science & Technology, Life Sciences & Biomedicine, Immunology, NATURAL-KILLER-CELLS, CHRONIC HEPATITIS-B, OXIDATIVE DNA-DAMAGE, ACTIVATING RECEPTOR NKG2D, NK CELLS, VIRUS INFECTION, PERSISTENT INFECTION, GLYCOPROTEIN UL16, SUPPRESSOR-CELLS, IMMUNE-SYSTEM
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inst for Liver and Digestive Hlth
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Surgical Biotechnology
URI: https://discovery.ucl.ac.uk/id/eprint/1534471
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