Publication date: Available online 5 February 2019
Source: Journal of Allergy and Clinical Immunology
Author(s): Sanjana Mahapatra, William T. Shearer, Charles G. Minard, Emily Mace, Mary Paul, Jordan S. Orange
Abstract
Background
Chronic human immunodeficiency virus (HIV) infection is known to trigger a population redistribution and alteration in the functional capacity of NK cells. Due to improved anti-retroviral treatments, there are rising numbers of adolescents and young adults worldwide that are living with HIV infection since birth.
Objective
We sought to determine how NK cell phenotypic and functional subsets are altered in treated pediatric patients.
Methods
NK cells were contrasted among 29 HIV-unexposed and uninfected controls (5-19 years), 23 HIV-exposed but uninfected patients (HEU) (3-19 years) and 25 HIV-infected patients (3-19 years) using multi-parametric flow cytometry.
Results
While majority of the NK cell markers did not differ, activating receptors like NKp46, DNAM-1, NKG2C and stimulatory receptors like CD2 and CD11c were expressed by a higher frequency of NK cells in HIV-infected patients than controls. Interestingly, there were less differences between HIV-infected and HEU children. There was an inverse relationship between CD4/CD8 T cell ratio (as a marker of disease progression) and CD11c and NKG2C frequency and CD69 upregulation on stimulation among HIV-infected patients.
Conclusions
A chronic NK cell activation phenotype persists in HIV-infected children receiving anti-retroviral therapy and is associated with declining CD4/CD8 T cell ratios. A lower CD4/CD8 T cell ratio was associated with higher baseline granzyme B (p=0.0068, R2=0.29) and degranulation potential (p=0.022, R2=0.22) in stimulated NK cells. Thus, NK cells in HIV-infected children receiving treatment have reduced functional potential and an activated phenotype that distinguishes them from uninfected children.
Graphical abstract
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