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(Auto)Antibody Responses Shape Memory NK Cell Pool Size and Composition.

Cristina Capuano1, Chiara Pighi1, Simone Battella1

  • 1Department of Experimental Medicine, Sapienza University of Rome, 00185 Roma, Italy.

Biomedicines
|March 25, 2022
PubMed
Summary
This summary is machine-generated.

Antibodies, particularly in human cytomegalovirus (HCMV) infection and immune thrombocytopenia (ITP), drive the expansion of memory NK cells. These cells, lacking FcεRIγ, show enhanced CD16-dependent functions.

Keywords:
CD16HCMVauto-antibodiesimmune thrombocytopenia (ITP)memory natural killer (NK) cells

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Area of Science:

  • Immunology
  • Virology
  • Cell Biology

Background:

  • Human cytomegalovirus (HCMV) infection induces adaptive immune responses, including the formation of memory Natural Killer (NK) cells.
  • Memory NK cells are characterized by Fc receptor gamma (FcεRIγ) deficiency and expression of NKG2C and CD57.
  • The role of CD16-mediated antibody signaling in shaping memory NK cell populations remains incompletely understood.

Purpose of the Study:

  • To investigate the ex vivo profile and in vitro responsiveness of memory NK cells to CD16 stimulation in HCMV-positive donors and immune thrombocytopenia (ITP) patients.
  • To determine the impact of opsonizing antibodies on the establishment and expansion of memory NK cell subsets.

Main Methods:

  • Flow cytometry analysis of NK cell subsets (FcεRIγ-, NKG2C+, CD57+) in healthy HCMV+ donors and ITP patients.
  • In vitro expansion assays using antibody-opsonized targets and ITP-derived platelets.
  • Assessment of CD16-dependent Interferon-gamma (IFNγ) production.

Main Results:

  • A specific FcεRIγ- NKG2C+CD57+ memory NK cell subset was identified, with abundance correlating with anti-HCMV antibody levels in healthy individuals.
  • This memory NK cell subset was significantly expanded in ITP patients, an antibody-mediated autoimmune disease.
  • These cells demonstrated robust and selective in vitro expansion upon stimulation with antibody-opsonized targets or ITP platelets, exhibiting superior CD16-dependent IFNγ production.

Conclusions:

  • Opsonizing antibodies are a critical host-dependent factor shaping the HCMV-driven memory NK cell compartment.
  • Chronic exposure to auto-antibodies contributes to the expansion of a specialized memory NK cell subset with distinct CD16-dependent functions.
  • The absence of the FcεRIγ chain confers enhanced responsiveness to CD16 engagement in NKG2C+CD57+ memory NK cells.