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Increased degranulation of natural killer cells during acute HCV correlates with the magnitude of virus-specific T cell responses

Pelletier, Sandy, Drouin, Christian, Bedard, Nathalie, Khakoo, Salim I., Bruneau, Julie and Shoukry, Naglaa H. (2010) Increased degranulation of natural killer cells during acute HCV correlates with the magnitude of virus-specific T cell responses Journal of Hepatology, 53, (5), pp. 805-816. (doi:10.1016/j.jhep.2010.05.013). (PMID:20688412).

Record type: Article

Abstract

Background & Aims
Natural killer (NK) cells provide early defense against viral infections by killing infected cells and producing cytokines that inhibit viral replication. NK cells also interact with dendritic cells (DCs) and this reciprocal interaction regulates both innate and adaptive immunity. Genetic studies have suggested that NK cell activity is a determinant of HCV infectious outcome but a functional correlation has not been established. We hypothesized that increased NK cell activity during acute HCV infection correlates with spontaneous viral clearance.

Methods
We used multiparametric flow cytometry to monitor longitudinally the phenotype and the activity of NK cells in a cohort of intravenous drug users following HCV exposure. Three groups were studied: acute HCV with chronic evolution (n = 13), acute resolving HCV (n = 11), and exposed un-infected individuals (n = 10). We examined the expression of several NK cell-activating and -inhibiting receptors, IFN-? production and CD107a degranulation upon stimulation, and the kinetics of NK cell responses relative to T cell responses.

Results
We observed decreased expression of the inhibitory NKG2A receptor in NK cells following spontaneous HCV clearance. In addition, we observed increased NK cell degranulation during acute HCV irrespective of infectious outcome. NK cell peak responses preceded or coincided with peak T cell responses. Furthermore, NK cell degranulation correlated with the magnitude of HCV-specific T cells.

Conclusions
Our results demonstrate that NK cells are activated during acute HCV regardless of infection outcome and may play an indirect role through induction and priming of T cell responses.

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More information

Published date: November 2010
Keywords: innate immunity, viral hepatitis, cytotoxicity, cytokines
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 336178
URI: http://eprints.soton.ac.uk/id/eprint/336178
ISSN: 0168-8278
PURE UUID: 954a3354-929d-4e5a-93b5-66cc4e6717ad

Catalogue record

Date deposited: 16 Mar 2012 13:43
Last modified: 18 Jul 2017 06:09

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Contributors

Author: Sandy Pelletier
Author: Christian Drouin
Author: Nathalie Bedard
Author: Salim I. Khakoo
Author: Julie Bruneau
Author: Naglaa H. Shoukry

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