Molecular Programming of Immunological Memory in Natural Killer Cells.
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.
Memorial Sloan Kettering Cancer Center, 408 East 69th Street, ZRC-1402, 10065, New York, NY, USA.
Aimee M
AM
Beaulieu
Sharline
S
Madera
Joseph C
JC
Sun
D056704:Adaptive Immunity; D000818:Animals; D049109:Cell Proliferation; D005786:Gene Expression Regulation; D006566:Herpesviridae Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000821:virology; D007156:Immunologic Memory / Q000235:genetics*; D007370:Interferon Type I / Q000235:genetics / Q000276:immunology; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology; D020382:Interleukin-18 / Q000235:genetics / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology / Q000821:virology; D051379:Mice; D018146:Muromegalovirus / Q000276:immunology; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*
D007370:Interferon Type I; D020382:Interleukin-18; D012097:Repressor Proteins; C406863:Rog protein, mouse; D018664:Interleukin-12