title: Enhanced natural killer-cell and T-cell responses to influenza A virus during pregnancy.
abstract: Pregnant women experience increased morbidity and mortality after influenza infection, for reasons that are not understood. Although some data suggest that natural killer (NK)- and T-cell responses are suppressed during pregnancy, influenza-specific responses have not been previously evaluated. Thus, we analyzed the responses of women that were pregnant (n = 21) versus those that were not (n = 29) immediately before inactivated influenza vaccination (IIV), 7 d after vaccination, and 6 wk postpartum. Expression of CD107a (a marker of cytolysis) and production of IFN-γ and macrophage inflammatory protein (MIP) 1β were assessed by flow cytometry. Pregnant women had a significantly increased percentage of NK cells producing a MIP-1β response to pH1N1 virus compared with nonpregnant women pre-IIV [median, 6.66 vs. 0.90% (P = 0.0149)] and 7 d post-IIV [median, 11.23 vs. 2.81% (P = 0.004)], indicating a heightened chemokine response in pregnant women that was further enhanced by the vaccination. Pregnant women also exhibited significantly increased T-cell production of MIP-1β and polyfunctionality in NK and T cells to pH1N1 virus pre- and post-IIV. NK- and T-cell polyfunctionality was also enhanced in pregnant women in response to the H3N2 viral strain. In contrast, pregnant women had significantly reduced NK- and T-cell responses to phorbol 12-myristate 13-acetate and ionomycin. This type of stimulation led to the conclusion that NK- and T-cell responses during pregnancy are suppressed, but clearly this conclusion is not correct relative to the more biologically relevant assays described here. Robust cellular immune responses to influenza during pregnancy could drive pulmonary inflammation, explaining increased morbidity and mortality.
authors.affiliation: Departments of Pediatrics, cblish@stanford.edu mmdavis@stanford.edu awkay@stanford.edu.
authors.forename: Alexander W
authors.initials: AW
authors.lastname: Kay
authors.affiliation: Statistics.
authors.forename: Julia
authors.initials: J
authors.lastname: Fukuyama
authors.affiliation: Obstetrics and Gynecology.
authors.forename: Natali
authors.initials: N
authors.lastname: Aziz
authors.affiliation: Departments of Pediatrics.
authors.forename: Cornelia L
authors.initials: CL
authors.lastname: Dekker
authors.affiliation: Departments of Pediatrics.
authors.forename: Sally
authors.initials: S
authors.lastname: Mackey
authors.affiliation: Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, CA 94305.
authors.forename: Gary E
authors.initials: GE
authors.lastname: Swan
authors.affiliation: Microbiology and Immunology, Immunology, and cblish@stanford.edu mmdavis@stanford.edu awkay@stanford.edu.
authors.forename: Mark M
authors.initials: MM
authors.lastname: Davis
authors.affiliation: Statistics.
authors.forename: Susan
authors.initials: S
authors.lastname: Holmes
authors.affiliation: Immunology, and Medicine, and cblish@stanford.edu mmdavis@stanford.edu awkay@stanford.edu.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Blish
mesh_terms: D000328:Adult; D054407:Chemokine CCL4 / Q000276:immunology / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology; D009980:Influenza A virus / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D015759:Ionomycin / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D052118:Lysosomal-Associated Membrane Protein 1 / Q000276:immunology / Q000378:metabolism; D049590:Postpartum Period / Q000276:immunology; D011247:Pregnancy; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D014611:Vaccination / Q000379:methods*; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology; D055815:Young Adult
chemical_list: D054407:Chemokine CCL4; D007252:Influenza Vaccines; D052118:Lysosomal-Associated Membrane Protein 1; D015164:Vaccines, Inactivated; D015759:Ionomycin; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate