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J Allergy Clin Immunol. 2019 Jul;144(1):294-303.e13. doi: 10.1016/j.jaci.2018.11.052. Epub 2019 Feb 5.

NK cells in treated HIV-infected children display altered phenotype and function.

Author information

1
Department of Pathology and Immunology, Baylor College of Medicine, Houston, Tex; Center for Human Immunobiology, Texas Children's Hospital, Houston, Tex.
2
Center for Human Immunobiology, Texas Children's Hospital, Houston, Tex; Department of Pediatrics, Baylor College of Medicine, Houston, Tex.
3
Department of Medicine, Baylor College of Medicine, Houston, Tex.
4
Department of Pediatrics, Baylor College of Medicine, Houston, Tex.
5
Department of Pathology and Immunology, Baylor College of Medicine, Houston, Tex; Center for Human Immunobiology, Texas Children's Hospital, Houston, Tex; Department of Pediatrics, Baylor College of Medicine, Houston, Tex. Electronic address: jso2121@cumc.columbia.edu.

Abstract

BACKGROUND:

Chronic HIV infection is known to trigger a population redistribution and alteration in the functional capacity of natural killer (NK) cells. Because of improved antiretroviral treatments, there are rising numbers of adolescents and young adults worldwide who 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 (3-19 years), and 25 HIV-infected patients (3-19 years) using multiparametric flow cytometry.

RESULTS:

Although most NK-cell markers did not differ, activating receptors such as NKp46, DNAX accessory molecule-1, and NKG2C and stimulatory receptors such as CD2 and CD11c were expressed by a higher frequency of NK cells in HIV-infected patients than in controls. Interestingly, there were less differences between HIV-infected and HIV-exposed but uninfected 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 antiretroviral 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 = .0068; R2 = 0.29) and degranulation potential (P = .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.

KEYWORDS:

NK cell; children; flow cytometry; treated HIV; vertical exposure

PMID:
30735686
DOI:
10.1016/j.jaci.2018.11.052

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