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The journal of immunology : official journal of the American Association of Immunologists v.198 no.3, 2017년, pp.1172 - 1182   SCI SCIE
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T Cells Infiltrating Diseased Liver Express Ligands for the NKG2D Stress Surveillance System

Huang, Wei-Chen (Division of Infection and Immunity, University College London, London WC1E 6JF, United Kingdom ) ; Easom, Nicholas J. (Division of Infection and Immunity, University College London, London WC1E 6JF, United Kingdom ) ; Tang, Xin-Zi (Division of Infection and Immunity, University College London, London WC1E 6JF, United Kingdom ) ; Gill, Upkar S. (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 ) ; Singh, Harsimran (Division of Infection and Immunity, University College London, London WC1E 6JF, United Kingdom ) ; Robertson, Francis (Department of Surgery and Interventional Science, University College London, London WC1E 6BT, United Kingdom ) ; Chang, Chiwen (Department of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom ) ; Trowsdale, John (and ) ; Davidson, Brian R. (Department of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom ) ; Rosenberg, William M. (and ) ; Fusai, Giuseppe (Institute for Liver and Digestive Health, University College London, London NW3 2PF, United Kingdom ) ; Toubert, Antoine (Institute for Liver and Digestive Health, ) ; Kennedy, Patrick T. ; Peppa, Dimitra ; Maini, Mala K. ;
  • 초록  

    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.


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