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Functional restoration of CD56(bright) NK cells facilitates immune control via IL-15 and NKG2D in patients under antiviral treatment for chronic hepatitis B

BACKGROUND AND AIMS: Hepatitis B virus (HBV) is intrinsically immunogenic, with long-lasting immune control in many patients. However, the mechanisms and key cell types underlying effective immune control are incompletely understood. METHODS: We studied the restoration of natural killer (NK) cell nu...

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Autores principales: Chen, Tao, Zhu, Lin, Shi, Aichao, Ding, Lin, Zhang, Xiaoping, Tan, Zhenmin, Guo, Wei, Yan, Weiming, Han, Meifang, Jia, Jidong, Luo, Xiaoping, Schuppan, Detlef, Ning, Qin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer India 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5606950/
https://www.ncbi.nlm.nih.gov/pubmed/28639033
http://dx.doi.org/10.1007/s12072-017-9803-4
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author Chen, Tao
Zhu, Lin
Shi, Aichao
Ding, Lin
Zhang, Xiaoping
Tan, Zhenmin
Guo, Wei
Yan, Weiming
Han, Meifang
Jia, Jidong
Luo, Xiaoping
Schuppan, Detlef
Ning, Qin
author_facet Chen, Tao
Zhu, Lin
Shi, Aichao
Ding, Lin
Zhang, Xiaoping
Tan, Zhenmin
Guo, Wei
Yan, Weiming
Han, Meifang
Jia, Jidong
Luo, Xiaoping
Schuppan, Detlef
Ning, Qin
author_sort Chen, Tao
collection PubMed
description BACKGROUND AND AIMS: Hepatitis B virus (HBV) is intrinsically immunogenic, with long-lasting immune control in many patients. However, the mechanisms and key cell types underlying effective immune control are incompletely understood. METHODS: We studied the restoration of natural killer (NK) cell numbers and function post antiviral treatment in 52 hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients who received telbivudine (LdT) for 48 weeks. Blood samples were collected at week 0, 12, 24, 36, and 48 and tested for HBV DNA, hepatitis B surface antigen (HBsAg), HBeAg, liver enzymes, and NK cell parameters. RESULTS: Compared with baseline, the number of peripheral CD3(−)CD56(bright) NK cells increased significantly from week 24 to 48, especially in patients with baseline alanine transaminase (ALT) two- to fivefold the upper line of normal (ULN) or HBV DNA <9 log(10) copies/ml. Expression (number and density) of activating receptors NKG2D and NKp46 on CD3(−)CD56(bright) NK cells was enhanced, while inhibitory receptor NKG2A decreased. Notably, numbers of CD3(−)CD56(bright) or NKG2D(+)CD3(−)CD56(bright) NK cells were significantly better restored in patients with HBeAg seroconversion. NK cell activating serum interleukin 15 (IL-15) was significantly increased during LdT treatment, especially in HBeAg seroconverters. LdT significantly enhanced expression of NKG2D and IL-15 in cultures of purified peripheral NK cells from treatment-naïve HBeAg-positive CHB patients. CONCLUSIONS: Functional restoration of CD56(bright) NK cells via upregulation of IL-15 and NKG2D is a novel activity of LdT and likely other antivirals, independent of its effect on HBV replication. This also demonstrates the importance of host immune restoration in controlling chronic HBV infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12072-017-9803-4) contains supplementary material, which is available to authorized users.
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spelling pubmed-56069502017-10-04 Functional restoration of CD56(bright) NK cells facilitates immune control via IL-15 and NKG2D in patients under antiviral treatment for chronic hepatitis B Chen, Tao Zhu, Lin Shi, Aichao Ding, Lin Zhang, Xiaoping Tan, Zhenmin Guo, Wei Yan, Weiming Han, Meifang Jia, Jidong Luo, Xiaoping Schuppan, Detlef Ning, Qin Hepatol Int Original Article BACKGROUND AND AIMS: Hepatitis B virus (HBV) is intrinsically immunogenic, with long-lasting immune control in many patients. However, the mechanisms and key cell types underlying effective immune control are incompletely understood. METHODS: We studied the restoration of natural killer (NK) cell numbers and function post antiviral treatment in 52 hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients who received telbivudine (LdT) for 48 weeks. Blood samples were collected at week 0, 12, 24, 36, and 48 and tested for HBV DNA, hepatitis B surface antigen (HBsAg), HBeAg, liver enzymes, and NK cell parameters. RESULTS: Compared with baseline, the number of peripheral CD3(−)CD56(bright) NK cells increased significantly from week 24 to 48, especially in patients with baseline alanine transaminase (ALT) two- to fivefold the upper line of normal (ULN) or HBV DNA <9 log(10) copies/ml. Expression (number and density) of activating receptors NKG2D and NKp46 on CD3(−)CD56(bright) NK cells was enhanced, while inhibitory receptor NKG2A decreased. Notably, numbers of CD3(−)CD56(bright) or NKG2D(+)CD3(−)CD56(bright) NK cells were significantly better restored in patients with HBeAg seroconversion. NK cell activating serum interleukin 15 (IL-15) was significantly increased during LdT treatment, especially in HBeAg seroconverters. LdT significantly enhanced expression of NKG2D and IL-15 in cultures of purified peripheral NK cells from treatment-naïve HBeAg-positive CHB patients. CONCLUSIONS: Functional restoration of CD56(bright) NK cells via upregulation of IL-15 and NKG2D is a novel activity of LdT and likely other antivirals, independent of its effect on HBV replication. This also demonstrates the importance of host immune restoration in controlling chronic HBV infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12072-017-9803-4) contains supplementary material, which is available to authorized users. Springer India 2017-06-20 /pmc/articles/PMC5606950/ /pubmed/28639033 http://dx.doi.org/10.1007/s12072-017-9803-4 Text en © The Author(s) 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Original Article
Chen, Tao
Zhu, Lin
Shi, Aichao
Ding, Lin
Zhang, Xiaoping
Tan, Zhenmin
Guo, Wei
Yan, Weiming
Han, Meifang
Jia, Jidong
Luo, Xiaoping
Schuppan, Detlef
Ning, Qin
Functional restoration of CD56(bright) NK cells facilitates immune control via IL-15 and NKG2D in patients under antiviral treatment for chronic hepatitis B
title Functional restoration of CD56(bright) NK cells facilitates immune control via IL-15 and NKG2D in patients under antiviral treatment for chronic hepatitis B
title_full Functional restoration of CD56(bright) NK cells facilitates immune control via IL-15 and NKG2D in patients under antiviral treatment for chronic hepatitis B
title_fullStr Functional restoration of CD56(bright) NK cells facilitates immune control via IL-15 and NKG2D in patients under antiviral treatment for chronic hepatitis B
title_full_unstemmed Functional restoration of CD56(bright) NK cells facilitates immune control via IL-15 and NKG2D in patients under antiviral treatment for chronic hepatitis B
title_short Functional restoration of CD56(bright) NK cells facilitates immune control via IL-15 and NKG2D in patients under antiviral treatment for chronic hepatitis B
title_sort functional restoration of cd56(bright) nk cells facilitates immune control via il-15 and nkg2d in patients under antiviral treatment for chronic hepatitis b
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5606950/
https://www.ncbi.nlm.nih.gov/pubmed/28639033
http://dx.doi.org/10.1007/s12072-017-9803-4
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