The impact of HIV-1 infection and exposure on natural killer (NK) cell phenotype in Kenyan infants during the first year of life
Open Access
- 1 January 2012
- journal article
- research article
- Published by Frontiers Media SA in Frontiers in Immunology
- Vol. 3, 37356
- https://doi.org/10.3389/fimmu.2012.00399
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.This publication has 65 references indexed in Scilit:
- NK cells in HIV‐1 infection: evidence for their role in the control of HIV‐1 infectionJournal of Internal Medicine, 2008
- Dysfunctional natural killer cells, in vivo, are governed by HIV viremia regardless of whether the infected individual is on antiretroviral therapyAIDS, 2007
- Natural Killer Cells in Perinatally HIV-1-Infected Children Exhibit Less Degranulation Compared to HIV-1-Exposed Uninfected Children and Their Expression of KIR2DL3, NKG2C, and NKp46 Correlates with Disease SeverityPublished by The American Association of Immunologists ,2007
- Evolution of Innate and Adaptive Effector Cell Functions during Acute HIV‐1 InfectionThe Journal of Infectious Diseases, 2007
- Low perforin and elevated SHIP-1 expression is associated with functional anergy of natural killer cells in chronic HIV-1 infectionAIDS, 2006
- Sequential deregulation of NK cell subset distribution and function starting in acute HIV-1 infectionBlood, 2005
- Dendritic and Natural Killer Cell Subsets Associated with Stable or Declining CD4+Cell Counts in Treated HIV‐1–Infected ChildrenThe Journal of Infectious Diseases, 2005
- Neonatal Natural Killer Cells Produce Chemokines and Suppress HIV Replicationin VitroAIDS Research and Human Retroviruses, 2004
- Increased Natural Killer Cell Activity in Viremic HIV-1 InfectionPublished by The American Association of Immunologists ,2004
- Sustained Impairment of IFN-γ Secretion in Suppressed HIV-Infected Patients Despite Mature NK Cell Recovery: Evidence for a Defective Reconstitution of Innate ImmunityThe Journal of Immunology, 2002