Journal
JOURNAL OF IMMUNOLOGY
Volume 198, Issue 3, Pages 1172-1182Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1601313
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Funding
- Wellcome Trust
- Ministry of National Defense/Medical Affairs Bureau, Taiwan
- Medical Research Council
- MRC [MR/M008614/1, MR/M020126/1, MR/M008614/2] Funding Source: UKRI
- Medical Research Council [MR/M020126/1, MR/M008614/2, MR/M008614/1] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0512-10124, 10/4001/11] Funding Source: researchfish
- Wellcome Trust [101849/Z/13/Z] Funding Source: researchfish
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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 HBVinfected 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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