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Blocking the Natural Killer (NK) Cell Inhibitory Receptor NKG2A Increases Activity of Human NK Cells and Clears HBV Infection in Mice.
Li F, Wei H, Wei H, Gao Y, Xu L, Yin W, Sun R, Tian Z.
SourceHefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui 230027, China.
Abstract
BACKGROUND & AIMS:: We studied the functions of natural killer (NK) cells and the role of the NK cell inhibitory receptor (NKG2A) during hepatitis B virus (HBV) infection in patients and mice. METHODS:: We analyzed levels of NKG2A on peripheral blood NK cells from 42 patients with active chronic hepatitis B (CHB), 31 patients with inactive CHB, and 35 healthy volunteers (controls). Five patients with CHB treated with anti-viral therapy were also included, to evaluate changes in NK cells after HBV titers decreased. We examined the effects of blocking antibodies against NKG2A, or its ligand Qa-1 (equivalent to HLA-E in humans), in immunocompetent mice that express HBV from a plasmid and are positive for serum hepatitis B surface antigen (a mouse model of HBV infection). RESULTS:: A higher percentage of NK cells from patients with active CHB were positive for NKG2A (38.47%) than from patients with inactive CHB (19.33%; P <.01) or controls (27.96%, P <.05). The percentage of NKG2A+ cells correlated with serum viral load (r=0.5457, P <.001). The percentage of NKG2A+ cells decreased along with HBV load in patients that received anti-viral therapy ( P <.05). Blocking NKG2A interaction with HLA-E in peripheral NK cells from patients with active CHB increased their cytotoxicity in vitro. NK cells of HBV carrier mice also had higher percentages of NK cells that expressed NKG2A compared with control mice; NKG2A was likely to be upregulated by production of interleukin-10 by hepatic regulatory CD4+CD25+ T cells. Blocking Qa-1 in these mice promoted viral clearance in an NK cell-dependent manner. CONCLUSIONS:: Infection with HBV increases levels of the inhibitory receptor NKG2A on NK cells in mice and humans, and reduces their ability to clear HBV. Reagents designed to block the interaction between NKG2A and HLA-E might be developed to treat CHB infection.
Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.
http://www.ncbi.nlm.nih.gov/pubmed/23103614 |
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楼主: cwy121
发表于 2012-11-15 18:19
