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

Area of Science:

• Immunology
• Virology
• Pediatrics

Background:

• Chronic HIV infection alters natural killer (NK) cell populations and function.
• Improved antiretroviral therapies (ART) increase the number of adolescents and young adults living with HIV since birth.

Purpose of the Study:

• To investigate alterations in NK-cell phenotypic and functional subsets in pediatric patients undergoing ART.

Main Methods:

• Multiparametric flow cytometry was used to compare NK cells from HIV-unexposed/uninfected controls, HIV-exposed/uninfected patients, and HIV-infected patients (ages 3-19 years).

Main Results:

• HIV-infected children showed higher frequencies of NK cells expressing activating receptors (NKp46, DNAX accessory molecule-1, NKG2C) and stimulatory receptors (CD2, CD11c) compared to controls.
• Fewer differences were observed between HIV-infected and HIV-exposed but uninfected children.
• An inverse relationship existed between the CD4/CD8 T-cell ratio and CD11c/NKG2C frequency and CD69 upregulation in HIV-infected patients.

Conclusions:

• A persistent chronic NK-cell activation phenotype is observed in HIV-infected children on ART, correlating with declining CD4/CD8 T-cell ratios.
• Lower CD4/CD8 T-cell ratios were associated with increased granzyme B and degranulation potential in stimulated NK cells.
• NK cells in treated HIV-infected children exhibit reduced functional potential and an activated phenotype compared to uninfected children.