Molecular Programming of Immunological Memory in Natural Killer Cells

  • Aimee M. Beaulieu
  • Sharline Madera
  • Joseph C. Sun
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 850)


Immunological memory is a hallmark of the adaptive immune system. Although natural killer (NK) cells have traditionally been classified as a component of the innate immune system, they have recently been shown in mice and humans to exhibit certain features of immunological memory, including an ability to undergo a clonal-like expansion during virus infection, generate long-lived progeny (i.e. memory cells), and mediate recall responses against previously encountered pathogens—all characteristics previously ascribed only to adaptive immune responses by B and T cells in mammals. To date, the molecular events that govern the generation of NK cell memory are not completely understood. Using a mouse model of cytomegalovirus infection, we demonstrate that individual pro-inflammatory IL-12, IL-18, and type I-IFN signaling pathways are indispensible and play non-redundant roles in the generation of virus-specific NK cell memory. Furthermore, we discovered that antigen-specific proliferation and protection by NK cells is mediated by the transcription factor Zbtb32, which is induced by pro-inflammatory cytokines and promotes a cell cycle program in activated NK cells. A greater understanding of the molecular mechanisms controlling NK cell responses will provide novel strategies for tailoring vaccines to target infectious disease.


Adaptive immune system Innate immune system NK cell memory Cytokine stimulation 


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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Aimee M. Beaulieu
    • 1
  • Sharline Madera
    • 1
  • Joseph C. Sun
    • 1
  1. 1.Memorial Sloan Kettering Cancer CenterNew YorkUSA

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