Sustained Immune Complex-Mediated Reduction in CD16 Expression after Vaccination Regulates NK Cell Function
Cross-linking of FcγRIII (CD16) by immune complexes induces antibody-dependent cellular cytotoxicity (ADCC) by natural killer (NK) cells, contributing to control of intracellular pathogens; this pathway can also be targeted for immunotherapy of cancerous or otherwise diseased cells. However, downreg...
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Published in | Frontiers in immunology Vol. 7; p. 384 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
Switzerland
Frontiers Media S.A
26.09.2016
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Subjects | |
Online Access | Get full text |
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Summary: | Cross-linking of FcγRIII (CD16) by immune complexes induces antibody-dependent cellular cytotoxicity (ADCC) by natural killer (NK) cells, contributing to control of intracellular pathogens; this pathway can also be targeted for immunotherapy of cancerous or otherwise diseased cells. However, downregulation of CD16 expression on activated NK cells may limit or regulate this response. Here, we report sustained downregulation of CD16 expression on NK cells
after intramuscular (but not intranasal) influenza vaccination. CD16 downregulation persisted for at least 12 weeks after vaccination and was associated with robust enhancement of influenza-specific plasma antibodies after intramuscular (but not intranasal) vaccination. This effect could be emulated
by co-culture of NK cells with influenza antigen and immune serum and, consistent with the sustained effects after vaccination, only very limited recovery of CD16 expression was observed during long-term
culture of immune complex-treated cells. CD16 downregulation was most marked among normally CD16
CD57
NK cells, irrespective of NKG2C expression, and was strongly positively associated with degranulation (surface CD107a expression). CD16 downregulation was partially reversed by inhibition of ADAM17 matrix metalloprotease, leading to a sustained increase in both CD107a and CD25 (IL-2Rα) expression. Both the degranulation and CD25 responses of CD57+ NK cells were uniquely dependent on trivalent influenza vaccine-specific IgG. These data support a role for CD16 in early activation of NK cells after vaccination and for CD16 downregulation as a means to modulate NK cell responses and maintain immune homeostasis of both antibody and T cell-dependent pathways. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Edited by: Emanuela Marcenaro, University of Genoa, Italy Reviewed by: Kasper Hoebe, The Cincinnati Children’s Hospital Medical Center, USA; Stephen Noel Waggoner, Cincinnati Children’s Hospital Medical Center, USA Specialty section: This article was submitted to NK Cell Biology, a section of the journal Frontiers in Immunology |
ISSN: | 1664-3224 1664-3224 |
DOI: | 10.3389/fimmu.2016.00384 |