title: Proinflammatory cytokine signaling required for the generation of natural killer cell memory.
abstract: Although natural killer (NK) cells are classified as innate immune cells, recent studies demonstrate that NK cells can become long-lived memory cells and contribute to secondary immune responses. The precise signals that promote generation of long-lived memory NK cells are unknown. Using cytokine receptor-deficient mice, we show that interleukin-12 (IL-12) is indispensible for mouse cytomegalovirus (MCMV)-specific NK cell expansion and generation of memory NK cells. In contrast to wild-type NK cells that proliferated robustly and resided in lymphoid and nonlymphoid tissues for months after MCMV infection, IL-12 receptor-deficient NK cells failed to expand and were unable to mediate protection after MCMV challenge. We further demonstrate that a STAT4-dependent IFN-γ-independent mechanism contributes toward the generation of memory NK cells during MCMV infection. Understanding the full contribution of inflammatory cytokine signaling to the NK cell response against viral infection will be of interest for the development of vaccines and therapeutics.
authors.affiliation: Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Sun
authors.forename: Sharline
authors.initials: S
authors.lastname: Madera
authors.forename: Natalie A
authors.initials: NA
authors.lastname: Bezman
authors.forename: Joshua N
authors.initials: JN
authors.lastname: Beilke
authors.forename: Mark H
authors.initials: MH
authors.lastname: Kaplan
authors.forename: Lewis L
authors.initials: LL
authors.lastname: Lanier
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D016207:Cytokines / Q000276:immunology*; D005434:Flow Cytometry; D006566:Herpesviridae Infections / Q000276:immunology*; D007156:Immunologic Memory / Q000276:immunology*; D018664:Interleukin-12 / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018146:Muromegalovirus / Q000276:immunology*; D053707:Receptors, Interleukin-12 / Q000235:genetics; D050797:STAT4 Transcription Factor / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D018709:Statistics, Nonparametric
chemical_list: D016207:Cytokines; C508443:Il12rb2 protein, mouse; D053707:Receptors, Interleukin-12; D050797:STAT4 Transcription Factor; C494091:Stat4 protein, mouse; D018664:Interleukin-12