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Molecular Programming of Immunological Memory in Natural Killer Cells

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Crossroads Between Innate and Adaptive Immunity V

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 850))

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.

Aimee M. Beaulieu and Sharline Madera contributed equally.

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Authors and Affiliations

  1. Memorial Sloan Kettering Cancer Center, 408 East 69th Street, ZRC-1402, 10065, New York, NY, USA

    Aimee M. Beaulieu, Sharline Madera & Joseph C. Sun PhD

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  1. Aimee M. Beaulieu
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  2. Sharline Madera
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  3. Joseph C. Sun PhD
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Editors and Affiliations

  1. Laboratory of Cellular Immunology, La Jolla Institute for Allergy and Immun, La Jolla, USA

    Stephen P. Schoenberger

  2. Department Microbiology & Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA

    Peter D. Katsikis

  3. Yerkes National Primate Research Center, Emory University Emory Vaccine Center &, Atlanta, Georgia, USA

    Bali Pulendran

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Beaulieu, A., Madera, S., Sun, J. (2015). Molecular Programming of Immunological Memory in Natural Killer Cells. In: Schoenberger, S., Katsikis, P., Pulendran, B. (eds) Crossroads Between Innate and Adaptive Immunity V. Advances in Experimental Medicine and Biology, vol 850. Springer, Cham. https://doi.org/10.1007/978-3-319-15774-0_7

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