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

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.