Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.746193
Title: NKG2D-dependent cross talk between NK cells and CD4 T cells in chronic hepatitis B
Author: Huang, W. C.
ISNI:       0000 0004 7230 330X
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2016
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Abstract:
NK cells are emerging as potent regulators of adaptive immunity in virus infection. Our group recently documented the partially TRAIL-dependent deletion of HBV-specific T cells by NK cells. For this study, we investigated the underlying interactions between NK cells and T cells through the NKG2D pathway in chronic HBV infection. In this study, we observed that activated and HBV-specific T cells, especially the CD4 fraction, expressed NKG2D ligands (NKG2D-L) not normally seen on T cells. NKG2D-L upregulation was further enriched on CD4 T cells in HBV-infected livers compared to the circulation and control livers. Oxidative stress, one noteworthy pathogenic feature of HBV infection, was demonstrated to recapitulate the T cell NKG2D-L upregulation pattern seen in patients with chronic hepatitis B (CHB). NK cells from patients with CHB maintained NKG2D expression and their increased activation and cytotoxicity could be driven by NKG2D-L expressing cells. In line with the distinctive features of T cells and NK cells in CHB, we discovered a positive correlation between activation of NKG2D+NK cells and the NKG2D-L (MICA/B) levels on CD4 T cells. Additionally, the pro-inflammatory cytokine IFN-α, used in HBV treatment, was shown to favour for NKG2D-mediated regulation. To conclude, we provide the first ex vivo evidence that human T cells, particularly those sequestered within tissues, can become visible to the stress surveillance system by the induction of NKG2D-L. We show that in active CHB, T cells upregulate NKG2D-L which can drive NK cell activation and cytotoxicity via the NKG2D pathway. These interactions may be triggered by aberrant oxidative stress and result in a homeostatic response of "damage removal", thereby limiting T cell antiviral immunity. Therefore, efforts to manipulate the HBV-infected liver milieu in order to decrease T cell oxidative stress and diminish constraints from NK cells and the NKG2D pathway should be considered to reduce HBV pathogenesis and promote immunity.
Supervisor: Maini, M. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.746193  DOI: Not available
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