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Sustained Immune Complex-Mediated Reduction in CD16 Expression after Vaccination Regulates NK Cell Function.

Martin R Goodier1, Chiara Lusa1, Sam Sherratt1

  • 1Department of Immunology and Infection, London School of Hygiene and Tropical Medicine , London , UK.

Frontiers in Immunology
|October 12, 2016
PubMed
Summary
This summary is machine-generated.

Intramuscular influenza vaccination causes sustained downregulation of FcγRIII (CD16) on natural killer (NK) cells, enhancing antibody responses. This CD16 modulation impacts NK cell activation and immune homeostasis.

Keywords:
CD16CD25CD57NK cellsdegranulationinfluenzavaccination

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Area of Science:

  • Immunology
  • Vaccinology

Background:

  • FcγRIII (CD16) cross-linking by immune complexes on natural killer (NK) cells triggers antibody-dependent cellular cytotoxicity (ADCC).
  • Downregulation of CD16 on activated NK cells can modulate immune responses, impacting immunotherapy and pathogen control.

Purpose of the Study:

  • To investigate the in vivo effects of influenza vaccination on CD16 expression in NK cells.
  • To understand the mechanisms and consequences of CD16 downregulation following vaccination.

Main Methods:

  • Intramuscular and intranasal influenza vaccination in vivo.
  • Co-culture of NK cells with influenza antigen and immune serum in vitro.
  • Flow cytometry analysis of CD16, CD57, NKG2C, CD107a, and CD25 expression.
  • Inhibition of ADAM17 metalloprotease.

Main Results:

  • Intramuscular, but not intranasal, influenza vaccination led to sustained CD16 downregulation on NK cells for at least 12 weeks.
  • CD16 downregulation was associated with enhanced influenza-specific antibody production.
  • CD16 downregulation was most prominent in CD16high CD57+ NK cells and positively correlated with degranulation (CD107a).
  • ADAM17 inhibition partially reversed CD16 downregulation and increased CD107a and CD25 expression.

Conclusions:

  • Sustained CD16 downregulation on NK cells after intramuscular influenza vaccination modulates NK cell responses.
  • This downregulation enhances antibody production and may contribute to immune homeostasis.
  • CD16 plays a role in early NK cell activation post-vaccination, with its downregulation serving as a regulatory mechanism.