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Review
. 2015:850:81-91.
doi: 10.1007/978-3-319-15774-0_7.

Molecular Programming of Immunological Memory in Natural Killer Cells

Aimee M Beaulieu  1 , Sharline Madera, Joseph C Sun
Affiliations
Review

Molecular Programming of Immunological Memory in Natural Killer Cells

Aimee M Beaulieu et al. Adv Exp Med Biol. 2015.

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.

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