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

TY - JOUR

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

N1 - © 2014 The Authors. Clinical & Experimental Immunology published by John Wiley & Sons Ltd on behalf of British Society for Immunology.

PY - 2015/3/1

Y1 - 2015/3/1

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.

KW - Adolescent

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

U2 - 10.1111/cei.12470

DO - 10.1111/cei.12470

M3 - Journal article

C2 - 25311087

SN - 0009-9104

VL - 179

SP - 466

EP - 476

JO - Clinical and Experimental Immunology

JF - Clinical and Experimental Immunology

IS - 3

ER -