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. 2014 May 15;28(8):1115-24.
doi: 10.1097/QAD.0000000000000263.

Natural killer cell and T-cell subset distributions and activation influence susceptibility to perinatal HIV-1 infection

Melanie A Gasper  1 , Pratima Kunwar, Grace Itaya, Nicholas Lejarcegui, Rose Bosire, Elizabeth Maleche-Obimbo, Dalton Wamalwa, Jennifer Slyker, Julie Overbaugh, Helen Horton, Donald L Sodora, Grace John-Stewart, Barbara Lohman-Payne
Affiliations

Natural killer cell and T-cell subset distributions and activation influence susceptibility to perinatal HIV-1 infection

Melanie A Gasper et al. AIDS. .

Abstract

Objective: To determine neonatal immunologic factors that correlate with mother-to-child-transmission of HIV-1.

Design: This case-control study compared cord blood natural killer (NK) and T-cell populations of HIV-1 exposed infants who subsequently acquired infection by 1 month (cases) to those who remained uninfected by 1 year of life (controls). Control specimens were selected by proportional match on maternal viral load.

Methods: Cryopreserved cord blood mononuclear cells (CBMCs) were thawed and stained for multiparameter flow cytometry to detect NK and T-cell subsets and activation status. CBMCs were also used in a viral suppression assay to evaluate NK cell inhibition of HIV-1 replication in autologous CD4 T cells.

Results: Cord blood from cases contained a skewed NK cell repertoire characterized by an increased proportion of CD16CD56 NK cells. In addition, cases displayed less-activated CD16CD56 NK cells and CD8 T cells, based on HLA-DRCD38 costaining. NK cell suppression of HIV-1 replication ex vivo correlated with the proportion of acutely activated CD68CD16CD56 NK cells. Finally, we detected a higher proportion of CD27CD45RA effector memory CD4 and CD8 T cells in cord blood from cases compared with controls.

Conclusion: When controlled for maternal viral load, cord blood from infants who acquired HIV-1 had a higher proportion of CD16CD56 NK cells, lower NK cell activation and higher levels of mature T cells (potential HIV-1 targets) than control infants who remained uninfected. Our data provide evidence that infant HIV-1 acquisition may be influenced by both innate and adaptive immune cell phenotypes and activation status.

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Conflict of interest statement

Conflicts of interest

The authors declare there are no conflicts of interest.

Figures

Fig. 1
Fig. 1. Natural killer cell frequency and subset distribution in cord blood of HIV-1 uninfected infants grouped by subsequent HIV-1 acquisition
Cord blood mononuclear cells were gated on singlets and live cells prior to exclusion of CD3+ and CD20+ lymphocytes. NK cells subsets were defined by the expression of surface markers CD56 and/or CD16 (a). The proportion of CD3−CD20− cells defined as NK cells found in cases and controls (b). The median frequencies of the phenotypic distribution of NK cell subsets shown for controls and cases (c). Detailed distribution of individual data points for comparison of NK cell subsets between controls and cases (d). Lines represent the medians for a given subset. Statistics were generated via a Mann–Whitney test (*P <0.05).
Fig. 2
Fig. 2. Natural killer cell activation status by subset
NK cell subsets were assessed for coexpression HLA-DR and CD38 (a) as indicators of chronic activation in cases and controls in CD16−CD56+, CD16+CD56+ and CD16+CD56− NK cells (b). Lines represent medians for a given subset. Statistics were generated via a Mann–Whitney test (*P <0.05; n.s. P >0.1).
Fig. 3
Fig. 3. Viral suppressive capacity of cord blood natural killer cells
NK cells were assessed for their ability to suppress HIV-1 replication in autologous CD4+ T cells (n = 26). Suppressive capacity was correlated with NK activation (CD69+ NK cells). Each point represents the average suppressive capacity of NK cells from each cord blood sample’s replicates. Solid dots represent infants who remained HIV-1 uninfected (controls) while ‘x’s’ represent infants who subsequently became HIV-1 infected (cases). Statistics were generated using a Spearman correlation.
Fig. 4
Fig. 4. CD4+ and CD8+ T-cell activation and maturation status in cryopreserved cord blood mononuclear cell by subsequent HIV-1 acquisition
CD4+ or CD8+ lymphocytes were assessed for activation and maturation status by expression of HLA-DR and CD38 (a, left) as well as CD27 and/or CD45RA (a, right). Activation of CD4+ (b, circles, left) and CD8+ (b, squares, right) T cells between cases and controls as well as the proportion of cells in maturation states (from left to right): effector memory (CD27−CD45RA−), naive (CD27+CD45RA+), central memory (CD27+CD45RA−) or effector (CD27−CD45RA+) CD4+ T cells (c) or CD8+ T cells (d). CD4+ T cells are represented by circles and CD8+ T cells are represented by squares; controls are open symbols, cases, closed symbols. Lines represent medians for each group, and statistics were generated using a Mann–Whitney test (*P <0.05, n.s. P >0.1).
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