title: DAP12 signaling directly augments proproliferative cytokine stimulation of NK cells during viral infections.
abstract: NK cells vigorously proliferate during viral infections. During the course of murine CMV infection, this response becomes dominated by the preferential proliferation of NK cells that express the activation receptor Ly49H. The factors driving such selective NK cell proliferation have not been characterized. In this study, we demonstrate that preferential NK cell proliferation is dependent on DAP12-mediated signaling following the binding of Ly49H to its virally encoded ligand, m157. Ly49H signaling through DAP12 appears to directly augment NK cell sensitivity to low concentrations of proproliferative cytokines such as IL-15. The impact of Ly49H-mediated signaling on NK cell proliferation is masked in the presence of high concentrations of proproliferative cytokines that nonselectively drive all NK cells to proliferate.
authors.affiliation: Division of Pediatric Rheumatology, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USA. french_a@kids.wustl.edu
authors.forename: Anthony R
authors.initials: AR
authors.lastname: French
authors.forename: Hanna
authors.initials: H
authors.lastname: Sjölin
authors.forename: Sungjin
authors.initials: S
authors.lastname: Kim
authors.forename: Rima
authors.initials: R
authors.lastname: Koka
authors.forename: Liping
authors.initials: L
authors.lastname: Yang
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Young
authors.forename: Cristina
authors.initials: C
authors.lastname: Cerboni
authors.forename: Elena
authors.initials: E
authors.lastname: Tomasello
authors.forename: Averil
authors.initials: A
authors.lastname: Ma
authors.forename: Eric
authors.initials: E
authors.lastname: Vivier
authors.forename: Klas
authors.initials: K
authors.lastname: Kärre
authors.forename: Wayne M
authors.initials: WM
authors.lastname: Yokoyama
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism / Q000502:physiology; D049109:Cell Proliferation; D016207:Cytokines / Q000502:physiology*; D006566:Herpesviridae Infections / Q000276:immunology; D019409:Interleukin-15 / Q000502:physiology; D007694:Killer Cells, Natural / Q000166:cytology / Q000378:metabolism*; D037181:Lectins, C-Type / Q000378:metabolism / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D018146:Muromegalovirus / Q000276:immunology; D055650:NK Cell Lectin-Like Receptor Subfamily A; D018121:Receptors, Cytokine / Q000378:metabolism; D055630:Receptors, NK Cell Lectin-Like; D015398:Signal Transduction; D014777:Virus Diseases / Q000276:immunology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000950:Antigens, Ly; D016207:Cytokines; D019409:Interleukin-15; C527096:Klra8 protein, mouse; D037181:Lectins, C-Type; D055650:NK Cell Lectin-Like Receptor Subfamily A; D018121:Receptors, Cytokine; D055630:Receptors, NK Cell Lectin-Like; C484963:Tyrobp protein, mouse