Plasmacytoid Dendritic Cells and CD8 T Cells From Pregnant Women Show Altered Phenotype and Function Following H1N1/09 Infection

Abstract

Pregnant women are a high-risk group during influenza pandemics. In this study we determined whether plasmacytoid dendritic cells (pDCs) and CD8 T cells from pregnant women display altered activity following in vitro infection with 2009 pandemic swine influenza (H1N1/09). Peripheral blood mononuclear cells (PBMCs) were isolated from pregnant (n = 26) and nonpregnant (n = 28) women. DC subtypes were enumerated from PBMCs. PBMCs were infected with H1N1/09 and CD86, human leukocyte antigen-DR (HLA-DR), and programmed death ligand 1/2 (PDL1/2) measured on pDCs. PD receptor 1 (PD1) was measured on CD8 T cells. Interferon-alpha (IFN-α), interleukin-2 (IL-2), tumor necrosis factor-alpha (TNFα), and IFN-gamma were measured from culture supernatant. pDC (ie, CD303(+)/CD1c(-) PBMCs) percentages were lower in pregnant compared with nonpregnant women (P < .05). Following H1N1/09 infection, pDCs from pregnant women showed higher expression of CD86 (P < .01), HLA-DR (P < .001), and PDL1 (P < .001) compared with nonpregnant women. Expression of PD1 on CD8 T cells was higher during pregnancy (P < .05). Following H1N1/09 infection, PBMCs from pregnant women displayed reduced IFN-α (P < .01), IL-2 (P < .01), and IFN-γ (P < .01) compared with nonpregnant women. Blocking PDL1 during H1N1/09 infection increased these cytokines during pregnancy (P < .05). Altered maternal cellular antiviral activity is implicated in the increased morbidity during pregnancy following influenza pandemics.