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J Immunol. 2019 Aug 19. pii: ji1801648. doi: 10.4049/jimmunol.1801648. [Epub ahead of print]
Influenza Vaccination Primes Human Myeloid Cell Cytokine Secretion and NK Cell Function.
Wagstaffe HR1, Pickering H2, Houghton J2, Mooney JP1,3, Wolf AS1,4, Prevatt N2, Behrens RH2, Holland MJ2, Riley EM1,3, Goodier MR5.
Author information
1 Department of Infection Biology, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom. 2 Department of Clinical Research, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom. 3 The Roslin Institute, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, United Kingdom; and. 4 Division of Infection and Immunity, University College London, London WC1E 6JF, United Kingdom. 5 Department of Infection Biology, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom; martin.goodier@lshtm.ac.uk.
Abstract
Cytokine-induced memory-like (CIML) NK cells generated in response to proinflammatory cytokines in vitro and in vivo can also be generated by vaccination, exhibiting heightened responses to cytokine stimulation months after their initial induction. Our previous study demonstrated that in vitro human NK cell responses to inactivated influenza virus were also indirectly augmented by very low doses of IL-15, which increased induction of myeloid cell-derived cytokine secretion. These findings led us to hypothesize that IL-15 stimulation could reveal a similar effect for active influenza vaccination and influence CIML NK cell effector functions. In this study, 51 healthy adults were vaccinated with seasonal influenza vaccine, and PBMC were collected before and up to 30 d after vaccination. Myeloid and lymphoid cell cytokine secretion was measured after in vitro PBMC restimulation with low-dose IL-15, alone or in combination with inactivated H3N2 virus; the associated NK cell response was assessed by flow cytometry. PBMC collected 30 d postvaccination showed heightened cytokine production in response to IL-15 compared with PBMC collected at baseline; these responses were further enhanced when IL-15 was combined with H3N2. NK cell activation in response to IL-15 alone (CD25) and H3N2 plus IL-15 (CD25 and IFN-γ) was enhanced postvaccination. We also observed proliferation of less-differentiated NK cells with downregulation of cytokine receptors as early as 3 d after vaccination, suggesting cytokine stimulation in vivo. We conclude that vaccination-induced "training" of accessory cells combines with the generation of CIML NK cells to enhance the overall NK cell response postvaccination.
Copyright ? 2019 by The American Association of Immunologists, Inc.
PMID: 31427444 DOI: 10.4049/jimmunol.1801648
Influenza Vaccination Primes Human Myeloid Cell Cytokine Secretion and NK Cell Function.
Wagstaffe HR1, Pickering H2, Houghton J2, Mooney JP1,3, Wolf AS1,4, Prevatt N2, Behrens RH2, Holland MJ2, Riley EM1,3, Goodier MR5.
Author information
1 Department of Infection Biology, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom. 2 Department of Clinical Research, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom. 3 The Roslin Institute, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, United Kingdom; and. 4 Division of Infection and Immunity, University College London, London WC1E 6JF, United Kingdom. 5 Department of Infection Biology, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom; martin.goodier@lshtm.ac.uk.
Abstract
Cytokine-induced memory-like (CIML) NK cells generated in response to proinflammatory cytokines in vitro and in vivo can also be generated by vaccination, exhibiting heightened responses to cytokine stimulation months after their initial induction. Our previous study demonstrated that in vitro human NK cell responses to inactivated influenza virus were also indirectly augmented by very low doses of IL-15, which increased induction of myeloid cell-derived cytokine secretion. These findings led us to hypothesize that IL-15 stimulation could reveal a similar effect for active influenza vaccination and influence CIML NK cell effector functions. In this study, 51 healthy adults were vaccinated with seasonal influenza vaccine, and PBMC were collected before and up to 30 d after vaccination. Myeloid and lymphoid cell cytokine secretion was measured after in vitro PBMC restimulation with low-dose IL-15, alone or in combination with inactivated H3N2 virus; the associated NK cell response was assessed by flow cytometry. PBMC collected 30 d postvaccination showed heightened cytokine production in response to IL-15 compared with PBMC collected at baseline; these responses were further enhanced when IL-15 was combined with H3N2. NK cell activation in response to IL-15 alone (CD25) and H3N2 plus IL-15 (CD25 and IFN-γ) was enhanced postvaccination. We also observed proliferation of less-differentiated NK cells with downregulation of cytokine receptors as early as 3 d after vaccination, suggesting cytokine stimulation in vivo. We conclude that vaccination-induced "training" of accessory cells combines with the generation of CIML NK cells to enhance the overall NK cell response postvaccination.
Copyright ? 2019 by The American Association of Immunologists, Inc.
PMID: 31427444 DOI: 10.4049/jimmunol.1801648