The impact of HIV-1 infection and exposure on natural killer (NK) cell phenotype in Kenyan infants during the first year of life

Abstract

Natural killer (NK) cells play an important role in the containment of HIV replication during primary infection, though their functions are impaired during chronic HIV infection. Infants experience more rapid HIV disease progression than adults, but contributions of infant NK cells to containing HIV infection are unknown. The aim of this study was to determine the impact of HIV infection on infant NK cell phenotype by evaluating samples and data from a cohort study of women and their infants, conducted in Nairobi, Kenya between 1999 and 2003. The percentage and phenotype of NK cells was evaluated longitudinally by multi-parameter flow cytometry over the first year of life in HIV-infected (HIV+, = 16), HIV-exposed uninfected (HIV-EU, n = 6), and healthy unexposed controls (HIV–, n = 4). At birth, NK subset distributions based on expression of CD56 and CD16 did not differ between HIV+, HIV-EU, or HIV– infants. However, HIV infection was associated with a subsequent decline in NK cells as a percentage of total lymphocytes (p < 0.001), and an expanding proportion of CD56-CD16+ NK cells (p < 0.001). Activated CD38brightCD69+ NK cells were more frequent in the HIV+ infants, followed by HIV-EU and HIV- infants, in both CD56dim (p = 0.005) and CD56bright compartments (p = 0.03). HIV infection and exposure was also associated with a significant decline in the percentage of perforin-expressing NK cells in the CD56dim compartment over the first year of life, with HIV+ infants losing approximately 2.5% (p < 0.001) and HIV-EU infants losing 3.0% (p = 0.01) of perforin+ cells per month. Thus, infant HIV infection is associated with alterations in NK cell subsets, activation, and cytolytic potential that could contribute to their poor control over HIV infection. Furthermore, exposure to HIV infection in infants who escaped infection is also associated with alterations in NK cells that may contribute to the reduced ability to fight infections that is observed in HIV-EU infants.

Altered Innate Immune Development in HIV-Exposed Uninfected Infants

“…Many of these observations have been in cord blood and these changes are no longer detected later in life. Functional comparison of natural killer (NK) cell activity at one month of age also demonstrates an increase of an intermediate NK phenotype for activation and perforin expression in HEU vs. UE, which ‘normalizes’ by one year 28 . These findings are in line with our observations at the cellular level.…”

High Prevalence of Tuberculosis Infection in HIV-1 Exposed Kenyan Infants

“…6 HIV-1 exposed children may have higher risk for TB due to increased exposure to active TB, impaired BCG vaccine responses, and alterations in innate and adaptive immunity that may affect TB susceptibility. 4,5,22 The IMPAACT 1041 trial detected latent TB among 2.6% of HIV-1 exposed children below 2 years using TST; however, this study excluded infants with known active TB contacts, had high incidence of active TB prior to 2 years, and did not assess earlier time-points for latent TB. Extrapolating from their observed 4.25% annual rate of active TB and assuming that 20–40% of infants with TB infection develop active TB, we estimate an annual rate of infant TB infection between 11 and 21%, consistent with our findings.…”

Increased CD16 expression on NK cells is indicative of antibody-dependent cell-mediated cytotoxicity in chronic-active antibody-mediated rejection

“…Using the combination of CD14 and CD16, classical (CD14 ++ CD16 − ), intermediate (CD14 + CD16 + ) and non-classical (CD14 + CD16 ++ ) monocytes were identified within PBMCs as described by Ziegler-Heitbrock et al [25]. The NK cells are identified as negative for CD3 and CD19 and positive for CD56 either co-expressing CD16 or not [26].…”