Altered Natural Killer Cell Function in HIV-Exposed Uninfected Infants

Area of Science:

• Immunology
• Pediatrics
• Infectious Diseases

Background:

• HIV-exposed uninfected (HEU) infants experience higher severe infection rates than HIV-unexposed (HUU) infants.
• Immune system perturbations are suspected contributors to increased susceptibility in HEU infants.

Purpose of the Study:

• To investigate potential alterations in natural killer (NK) cell activity in HEU infants.
• To determine if NK cell dysfunction contributes to increased infection risk in HEU infants.

Main Methods:

• A case-control study compared NK cell phenotype and function in HEU and HUU infants at birth and 6 months.
• Flow cytometry assessed NK cell activity, including cytotoxicity against K562 cells, degranulation (CD107a), and cytokine production (IFNγ).

Main Results:

• HEU infants had lower NK cell proportions at birth and 6 months compared to HUU infants.
• At birth, HEU NK cells showed increased cytotoxicity and degranulation but reduced IFNγ production; these differences normalized by 6 months, except for reduced IFNγ and perforin.
• Lower NK cell activity in HEU infants was linked to reduced IL-12, IL-15, and IL-18; exogenous IL-12 restored IFNγ production.

Conclusions:

• NK cell proportion, phenotype, and function are altered in HEU infants, with reduced functional reserve.
• Impaired IL-12 production by accessory cells may contribute to NK cell dysfunction in HEU infants.
• Altered NK cell and accessory cell function likely contribute to the increased susceptibility to infections observed in HEU infants.