title: Impaired NK Cell Responses to Pertussis and H1N1 Influenza Vaccine Antigens in Human Cytomegalovirus-Infected Individuals.
abstract: NK cells contribute to postvaccination immune responses after activation by IL-2 from Ag-specific memory T cells or by cross-linking of the low-affinity IgG receptor, CD16, by Ag-Ab immune complexes. Sensitivity of NK cells to these signals from the adaptive immune system is heterogeneous and influenced by their stage of differentiation. CD56(dim)CD57(+) NK cells are less responsive to IL-2 and produce less IFN-γ in response to T cell-mediated activation than do CD56(bright) or CD56(dim)CD57(-) NK cells. Conversely, NK cell cytotoxicity, as measured by degranulation, is maintained across the CD56(dim) subsets. Human CMV (HCMV), a highly prevalent herpes virus causing lifelong, usually latent, infections, drives the expansion of the CD56(dim)CD57(+)NKG2C(+) NK cell population, skewing the NK cell repertoire in favor of cytotoxic responses at the expense of cytokine-driven responses. We hypothesized, therefore, that HCMV seropositivity would be associated with altered NK cell responses to vaccine Ags. In a cross-sectional study of 152 U.K. adults, with HCMV seroprevalence rate of 36%, we find that HCMV seropositivity is associated with lower NK cell IFN-γ production and degranulation after in vitro restimulation with pertussis or H1N1 influenza vaccine Ags. Higher expression of CD57/NKG2C and lower expression of IL-18Rα on NK cells from HCMV seropositive subjects do not fully explain these impaired responses, which are likely the result of multiple receptor-ligand interactions. This study demonstrates for the first time, to our knowledge, that HCMV serostatus influences NK cell contributions to adaptive immunity and raises important questions regarding the impact of HCMV infection on vaccine efficacy.
authors: Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom; and.
authors: Carolyn M
authors: CM
authors: Nielsen
authors: Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom; and.
authors: Matthew J
authors: MJ
authors: White
authors: Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom.
authors: Christian
authors: C
authors: Bottomley
authors: Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom; and.
authors: Chiara
authors: C
authors: Lusa
authors: Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom; and.
authors: Ana
authors: A
authors: Rodríguez-Galán
authors: Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom; and.
authors: Scarlett E G
authors: SE
authors: Turner
authors: Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom; and.
authors: Martin R
authors: MR
authors: Goodier
authors: Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom; and eleanor.riley@lshtm.ac.uk.
authors: Eleanor M
authors: EM
authors: Riley
mesh_terms: D000328:Adult; D000368:Aged; D003430:Cross-Sectional Studies; D003587:Cytomegalovirus / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010567:Pertussis Vaccine / Q000276:immunology*; D016036:Seroepidemiologic Studies; D055815:Young Adult
chemical_list: D007252:Influenza Vaccines; D010567:Pertussis Vaccine