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

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 CD16(-)CD56(+) NK cells. In addition, cases displayed less-activated CD16(-)CD56(+) NK cells and CD8(+) T cells, based on HLA-DR(+)CD38(+) costaining. NK cell suppression of HIV-1 replication ex vivo correlated with the proportion of acutely activated CD68(+)CD16(-)CD56(+) NK cells. Finally, we detected a higher proportion of CD27(-)CD45RA(-) 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 CD16(-)CD56(+) 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.