T Cells Infiltrating Diseased Liver Express Ligands for the NKG2D Stress Surveillance System.
J Immunol
; 198(3): 1172-1182, 2017 02 01.
Article
en En
| MEDLINE
| ID: mdl-28031333
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Células Asesinas Naturales
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Linfocitos T CD4-Positivos
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Hepatitis B Crónica
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Subfamilia K de Receptores Similares a Lectina de Células NK
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Hígado
Tipo de estudio:
Screening_studies
Límite:
Adult
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Female
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Humans
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Male
Idioma:
En
Revista:
J Immunol
Año:
2017
Tipo del documento:
Article
País de afiliación:
Reino Unido