Defective natural killer cell anti-viral capacity in paediatric HBV infection

I L Heiberg; L J Pallett; T N Winther; B Høgh; M K Maini; D Peppa

doi:10.1111/cei.12470

Defective natural killer cell anti-viral capacity in paediatric HBV infection

I L Heiberg, L J Pallett, T N Winther, B Høgh, M K Maini, D Peppa

16 Citationer (Scopus)

Abstract

Natural killer (NK) cells exhibit dysregulated effector function in adult chronic hepatitis B virus (HBV) infection (CHB), which may contribute to virus persistence. The role of NK cells in children infected perinatally with HBV is less studied. Access to a unique cohort enabled the cross-sectional evaluation of NK cell frequency, phenotype and function in HBV-infected children relative to uninfected children. We observed a selective defect in NK cell interferon (IFN)-γ production, with conserved cytolytic function, mirroring the functional dichotomy observed in adult infection. Reduced expression of NKp30 on NK cells suggests a role of impaired NK-dendritic cell (DC) cellular interactions as a potential mechanism leading to reduced IFN-γ production. The finding that NK cells are already defective in paediatric CHB, albeit less extensively than in adult CHB, has potential implications for the timing of anti-viral therapy aiming to restore immune control.

Originalsprog	Engelsk
Tidsskrift	Clinical and Experimental Immunology
Vol/bind	179
Udgave nummer	3
Sider (fra-til)	466-76
Antal sider	11
ISSN	0009-9104
DOI	https://doi.org/10.1111/cei.12470
Status	Udgivet - 1 mar. 2015

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10.1111/cei.12470Licens: CC BY

cei.12470Forlagets udgivne version, 300 KBLicens: CC BY

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abstract = "Natural killer (NK) cells exhibit dysregulated effector function in adult chronic hepatitis B virus (HBV) infection (CHB), which may contribute to virus persistence. The role of NK cells in children infected perinatally with HBV is less studied. Access to a unique cohort enabled the cross-sectional evaluation of NK cell frequency, phenotype and function in HBV-infected children relative to uninfected children. We observed a selective defect in NK cell interferon (IFN)-γ production, with conserved cytolytic function, mirroring the functional dichotomy observed in adult infection. Reduced expression of NKp30 on NK cells suggests a role of impaired NK-dendritic cell (DC) cellular interactions as a potential mechanism leading to reduced IFN-γ production. The finding that NK cells are already defective in paediatric CHB, albeit less extensively than in adult CHB, has potential implications for the timing of anti-viral therapy aiming to restore immune control. ",

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T1 - Defective natural killer cell anti-viral capacity in paediatric HBV infection

AU - Heiberg, I L

AU - Pallett, L J

AU - Winther, T N

AU - Høgh, B

AU - Maini, M K

AU - Peppa, D

PY - 2015/3/1

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N2 - Natural killer (NK) cells exhibit dysregulated effector function in adult chronic hepatitis B virus (HBV) infection (CHB), which may contribute to virus persistence. The role of NK cells in children infected perinatally with HBV is less studied. Access to a unique cohort enabled the cross-sectional evaluation of NK cell frequency, phenotype and function in HBV-infected children relative to uninfected children. We observed a selective defect in NK cell interferon (IFN)-γ production, with conserved cytolytic function, mirroring the functional dichotomy observed in adult infection. Reduced expression of NKp30 on NK cells suggests a role of impaired NK-dendritic cell (DC) cellular interactions as a potential mechanism leading to reduced IFN-γ production. The finding that NK cells are already defective in paediatric CHB, albeit less extensively than in adult CHB, has potential implications for the timing of anti-viral therapy aiming to restore immune control.

AB - Natural killer (NK) cells exhibit dysregulated effector function in adult chronic hepatitis B virus (HBV) infection (CHB), which may contribute to virus persistence. The role of NK cells in children infected perinatally with HBV is less studied. Access to a unique cohort enabled the cross-sectional evaluation of NK cell frequency, phenotype and function in HBV-infected children relative to uninfected children. We observed a selective defect in NK cell interferon (IFN)-γ production, with conserved cytolytic function, mirroring the functional dichotomy observed in adult infection. Reduced expression of NKp30 on NK cells suggests a role of impaired NK-dendritic cell (DC) cellular interactions as a potential mechanism leading to reduced IFN-γ production. The finding that NK cells are already defective in paediatric CHB, albeit less extensively than in adult CHB, has potential implications for the timing of anti-viral therapy aiming to restore immune control.

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KW - Antigens, Viral/immunology

KW - Cell Communication

KW - Child

KW - Child, Preschool

KW - Cohort Studies

KW - Cross-Sectional Studies

KW - Cytotoxicity, Immunologic

KW - Dendritic Cells/immunology

KW - Down-Regulation

KW - Female

KW - Hepatitis B/immunology

KW - Hepatitis B virus/immunology

KW - Humans

KW - Interferon-gamma/metabolism

KW - Killer Cells, Natural/immunology

KW - Male

KW - Natural Cytotoxicity Triggering Receptor 3/genetics

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DO - 10.1111/cei.12470

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VL - 179

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EP - 476

JO - Clinical and Experimental Immunology

JF - Clinical and Experimental Immunology

IS - 3

ER -

Defective natural killer cell anti-viral capacity in paediatric HBV infection

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