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Huang, Wei-Chen; Easom, Nicholas J.; Tang, Xin-Zi; Gill, Upkar S.; Singh, Harsimran; Robertson, Francis; Chang, Chiwen; Trowsdale, John; Davidson, Brian R.; Rosenberg, William M.; Fusai, Giuseppe; Toubert, Antoine; Kennedy, Patrick T.; Peppa, Dimitra; Maini, Mala K.

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

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  • Medientyp: E-Artikel
  • Titel: T Cells Infiltrating Diseased Liver Express Ligands for the NKG2D Stress Surveillance System
  • Beteiligte: Huang, Wei-Chen; Easom, Nicholas J.; Tang, Xin-Zi; Gill, Upkar S.; Singh, Harsimran; Robertson, Francis; Chang, Chiwen; Trowsdale, John; Davidson, Brian R.; Rosenberg, William M.; Fusai, Giuseppe; Toubert, Antoine; Kennedy, Patrick T.; Peppa, Dimitra; Maini, Mala K.
  • Erschienen: The American Association of Immunologists, 2017
  • Erschienen in: The Journal of Immunology, 198 (2017) 3, Seite 1172-1182
  • Sprache: Englisch
  • DOI: 10.4049/jimmunol.1601313
  • ISSN: 0022-1767; 1550-6606
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: 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.
  • Zugangsstatus: Freier Zugang