title: Influenza Vaccination Generates Cytokine-Induced Memory-like NK Cells: Impact of Human Cytomegalovirus Infection.
abstract: Human NK cells are activated by cytokines, immune complexes, and signals transduced via activating ligands on other host cells. After vaccination, or during secondary infection, adaptive immune responses can enhance both cytokine-driven and Ab-dependent NK cell responses. However, induction of NK cells for enhanced function after in vitro exposure to innate inflammatory cytokines has also been reported and may synergize with adaptive signals to potentiate NK cell activity during infection or vaccination. To test this hypothesis, we examined the effect of seasonal influenza vaccination on NK cell function and phenotype in 52 previously unvaccinated individuals. Enhanced, IL-2-dependent, NK cell IFN-γ responses to Influenza A/California/7/2009 virus were detected up to 4 wk postvaccination and higher in human CMV (HCMV)-seronegative (HCMV(-)) individuals than in HCMV-seropositive (HCMV(+)) individuals. By comparison, robust NK cell degranulation responses were observed both before and after vaccination, due to high titers of naturally occurring anti-influenza Abs in human plasma, and did not differ between HCMV(+) and HCMV(-) subjects. In addition to these IL-2-dependent and Ab-dependent responses, NK cell responses to innate cytokines were also enhanced after influenza vaccination; this was associated with proliferation of CD57(-) NK cells and was most evident in HCMV(+) subjects. Similar enhancement of cytokine responsiveness was observed when NK cells were cocultured in vitro with Influenza A/California/7/2009 virus, and this was at least partially dependent upon IFN-αβR2. In summary, our data indicate that attenuated or live viral vaccines promote cytokine-induced memory-like NK cells and that this process is influenced by HCMV infection.
authors.affiliation: Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom;
authors.forename: Martin R
authors.identifier: 0000-0002-8963-4768
authors.initials: MR
authors.lastname: Goodier
authors.affiliation: Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom;
authors.forename: Ana
authors.initials: A
authors.lastname: Rodriguez-Galan
authors.affiliation: Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom;
authors.forename: Chiara
authors.identifier: 0000-0003-3838-2203
authors.initials: C
authors.lastname: Lusa
authors.affiliation: Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom;
authors.forename: Carolyn M
authors.identifier: 0000-0002-9033-1318
authors.initials: CM
authors.lastname: Nielsen
authors.affiliation: Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom; MRC International Nutrition Group, Medical Research Council, The Gambia Unit, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom; and.
authors.forename: Alansana
authors.identifier: 0000-0002-1152-8156
authors.initials: A
authors.lastname: Darboe
authors.affiliation: Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom;
authors.forename: Ana L
authors.identifier: 0000-0003-4530-043X
authors.initials: AL
authors.lastname: Moldoveanu
authors.affiliation: Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom;
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: White
authors.affiliation: Department of Clinical Research, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom.
authors.forename: Ron
authors.identifier: 0000-0002-8166-2633
authors.initials: R
authors.lastname: Behrens
authors.affiliation: Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom; eleanor.riley@lshtm.ac.uk.
authors.forename: Eleanor M
authors.identifier: 0000-0003-3447-3570
authors.initials: EM
authors.lastname: Riley
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000150:complications / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D007252:Influenza Vaccines / Q000276:immunology*; D007251:Influenza, Human / Q000150:complications / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D008875:Middle Aged; D009975:Orthomyxoviridae / Q000276:immunology*; D014611:Vaccination; D055815:Young Adult
chemical_list: D007252:Influenza Vaccines; D007376:Interleukin-2; D007371:Interferon-gamma