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

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 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.

Natural killer cells in HIV-1 infection and therapy

“…Under homeostatic condition and in the absence of other viral infections, this population of CD56 neg NK cells is either not detectable or present at very low frequency [21–29]. The distribution and activation of NK cell subsets is relevant also in the context of mother-to-child HIV-1 transmission as they influence the susceptibility to perinatal infection [30]. …”

Defective Monocyte Enzymatic Function and an Inhibitory Immune Phenotype in Human Immunodeficiency Virus-Exposed Uninfected African Infants in the Era of Antiretroviral Therapy

“…Taken together, these result in a more permissive state for the development of infections [ 1 ]. Many observational studies reported immunological abnormalities in HEU infants [ 14 ] including highly differentiated T-cell [ 15 ] and B-cell subsets [ 16 ], altered responses to vaccines [ 17 ], functional impairment of natural killer cells [ 18 ], and monocytes [ 19 ]. Furthermore, few studies considered early transmission of immunomodulatory human herpes virus (HHV), cytomegalovirus (CMV) [ 20 ], and/or Epstein-Barr virus (EBV) [ 21 ] recrudescence during pregnancy, because HHVs are important drivers of inflammation in HEU infants [ 20 ].…”

Defective monocyte enzymatic function and an inhibitory immune phenotype in HIV-exposed uninfected African infants in the era of anti-retroviral therapy

“…Together these result in a more permissive state for the development of infections 1 . Many observational studies have reported immunological abnormalities in HEU infants 22 including highly differentiated T-cells [23][24][25][26][27][28][29] and B-cell subsets 30 , altered responses to vaccines [31][32][33] , functional impairment of natural killer cells 34 and monocytes [35][36][37] . Furthermore, few studies have considered early transmission of immunomodulatory human herpes virus' (HHVs), cytomegalovirus (CMV) 38 and Epstein Barr virus (EBV) 39 recrudescence during pregnancy on HEU immunity.…”