title: T Cells Infiltrating Diseased Liver Express Ligands for the NKG2D Stress Surveillance System.
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.
authors.affiliation: Division of Infection and Immunity, University College London, London WC1E 6JF, United Kingdom.|Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan.
authors.forename: Wei-Chen
authors.identifier: 0000-0002-9736-9933
authors.initials: WC
authors.lastname: Huang
authors.affiliation: Division of Infection and Immunity, University College London, London WC1E 6JF, United Kingdom.
authors.forename: Nicholas J
authors.identifier: 0000-0001-6413-919X
authors.initials: NJ
authors.lastname: Easom
authors.affiliation: Division of Infection and Immunity, University College London, London WC1E 6JF, United Kingdom.
authors.forename: Xin-Zi
authors.identifier: 0000-0001-6064-8624
authors.initials: XZ
authors.lastname: Tang
authors.affiliation: Centre for Immunobiology, Blizard Institute, Bart's and the London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, United Kingdom.
authors.forename: Upkar S
authors.initials: US
authors.lastname: Gill
authors.affiliation: Division of Infection and Immunity, University College London, London WC1E 6JF, United Kingdom.|Institute for Liver and Digestive Health, University College London, London NW3 2PF, United Kingdom.
authors.forename: Harsimran
authors.initials: H
authors.lastname: Singh
authors.affiliation: Department of Surgery and Interventional Science, University College London, London WC1E 6BT, United Kingdom.
authors.forename: Francis
authors.identifier: 0000-0001-5016-5944
authors.initials: F
authors.lastname: Robertson
authors.affiliation: Department of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom; and.
authors.forename: Chiwen
authors.initials: C
authors.lastname: Chang
authors.affiliation: Department of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom; and.
authors.forename: John
authors.initials: J
authors.lastname: Trowsdale
authors.affiliation: Institute for Liver and Digestive Health, University College London, London NW3 2PF, United Kingdom.|Department of Surgery and Interventional Science, University College London, London WC1E 6BT, United Kingdom.
authors.forename: Brian R
authors.initials: BR
authors.lastname: Davidson
authors.affiliation: Institute for Liver and Digestive Health, University College London, London NW3 2PF, United Kingdom.
authors.forename: William M
authors.identifier: 0000-0002-2732-2304
authors.initials: WM
authors.lastname: Rosenberg
authors.affiliation: Institute for Liver and Digestive Health, University College London, London NW3 2PF, United Kingdom.|Department of Surgery and Interventional Science, University College London, London WC1E 6BT, United Kingdom.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Fusai
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, INSERM UMRS 1160, AP-HP, Hôpital Saint-Louis, Paris 75013, France.
authors.forename: Antoine
authors.identifier: 0000-0002-7308-7317
authors.initials: A
authors.lastname: Toubert
authors.affiliation: Centre for Immunobiology, Blizard Institute, Bart's and the London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, United Kingdom.
authors.forename: Patrick T
authors.initials: PT
authors.lastname: Kennedy
authors.affiliation: Division of Infection and Immunity, University College London, London WC1E 6JF, United Kingdom.
authors.forename: Dimitra
authors.initials: D
authors.lastname: Peppa
authors.affiliation: Division of Infection and Immunity, University College London, London WC1E 6JF, United Kingdom; m.maini@ucl.ac.uk.
authors.forename: Mala K
authors.initials: MK
authors.lastname: Maini
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002450:Cell Communication; D002478:Cells, Cultured; D005260:Female; D019694:Hepatitis B, Chronic / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008024:Ligands; D008099:Liver / Q000276:immunology* / Q000821:virology; D008213:Lymphocyte Activation; D008297:Male; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: C527085:KLRK1 protein, human; D008024:Ligands; D055655:NK Cell Lectin-Like Receptor Subfamily K