Molecular programming of immunological memory in natural killer cells

Aimee Beaulieu, Sharline Madera, Joseph C. Sun

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)81-91
Number of pages11
JournalAdvances in experimental medicine and biology
Volume850
DOIs
Publication statusPublished - Jan 1 2015

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All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Keywords

  • Adaptive immune system
  • Cytokine stimulation
  • Innate immune system
  • NK cell memory

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