Impaired NK Cell Responses to Pertussis and H1N1 Influenza Vaccine Antigens in Human Cytomegalovirus-Infected Individuals
| Autor: | Matthew J. White, Chiara Lusa, Ana Rodriguez-Galan, Eleanor M. Riley, Christian Bottomley, Carolyn M. Nielsen, Scarlett E. G. Turner, Martin R. Goodier |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Human cytomegalovirus
Adult Male Immunology Population Cytomegalovirus CD16 Biology Interleukin 21 Young Adult Immune system Influenza A Virus H1N1 Subtype Antigen Recognition and Responses Seroepidemiologic Studies medicine Immunology and Allergy Cytotoxic T cell Humans education Aged Pertussis Vaccine education.field_of_study Degranulation Middle Aged medicine.disease Acquired immune system Flow Cytometry Virology 3. Good health Killer Cells Natural Cross-Sectional Studies Influenza Vaccines Cytomegalovirus Infections Female |
| Zdroj: | The Journal of Immunology Author Choice |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | 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. CD56dimCD57+ NK cells are less responsive to IL-2 and produce less IFN-γ in response to T cell–mediated activation than do CD56bright or CD56dimCD57− NK cells. Conversely, NK cell cytotoxicity, as measured by degranulation, is maintained across the CD56dim subsets. Human CMV (HCMV), a highly prevalent herpes virus causing lifelong, usually latent, infections, drives the expansion of the CD56dimCD57+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. |
| Databáze: | OpenAIRE |
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