title: Acute Virus Control Mediated by Licensed NK Cells Sets Primary CD8+ T Cell Dependence on CD27 Costimulation.
abstract: NK cells represent a critical first-line of immune defense against a bevy of viral pathogens, and infection can provoke them to mediate supportive and suppressive effects on virus-specific adaptive immunity. In mice expressing MHC class I Dk(Dk), a major murine CMV (MCMV) resistance factor and self-ligand of the inhibitory Ly49G2 (G2) receptor, licensed G2+NK cells provide essential host resistance against MCMV infection. Additionally G2+NK cell responses to MCMV increase the rate and extent of dendritic cell (DC) recovery, as well as early priming of CD8+T cell effectors in response to MCMV. However, relatively little is known about the NK cell effect on costimulatory ligand patterns displayed by DCs or on ensuing effector and memory T cell responses. In this study, we found that CD27-dependent CD8+T cell priming and differentiation are shaped by the efficiency of NK responses to virus infection. Surprisingly, differences in specific NK responses to MCMV in Dk-disparate mice failed to distinguish early DC costimulatory patterns. Nonetheless, although CD27 deficiency did not impede licensed NK-mediated resistance, CD70 and CD27 were required to efficiently prime and regulate effector CD8+T cell differentiation in response to MCMV, which eventually resulted in biased memory T cell precursor formation in Dkmice. In contrast, CD8+T cells accrued more slowly in non-Dkmice and eventually differentiated into terminal effector cells regardless of CD27 stimulation. Disparity in this requirement for CD27 signaling indicates that specific virus control mediated by NK cells can shape DC costimulatory signals needed to prime CD8+T cells and eventual T cell fate decisions.
authors: Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine, Charlottesville, VA 22908.|Beirne B. Carter Center for Immunology Research, University of Virginia School of Medicine, Charlottesville, VA 22908.
authors: Jeffrey J
authors: 0000-0002-9654-4277
authors: JJ
authors: Teoh
authors: Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine, Charlottesville, VA 22908.|Beirne B. Carter Center for Immunology Research, University of Virginia School of Medicine, Charlottesville, VA 22908.
authors: Awndre E
authors: AE
authors: Gamache
authors: Beirne B. Carter Center for Immunology Research, University of Virginia School of Medicine, Charlottesville, VA 22908.|Division of Nephrology, Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA 22908.
authors: Alyssa L
authors: AL
authors: Gillespie
authors: Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine, Charlottesville, VA 22908.|Beirne B. Carter Center for Immunology Research, University of Virginia School of Medicine, Charlottesville, VA 22908.
authors: Michael D
authors: MD
authors: Stadnisky
authors: Department of Immunology, Juntendo University School of Medicine, Tokyo 113-8421, Japan; and.
authors: Hideo
authors: H
authors: Yagita
authors: Beirne B. Carter Center for Immunology Research, University of Virginia School of Medicine, Charlottesville, VA 22908.|Department of Pathology, University of Virginia School of Medicine, Charlottesville, VA 22908.
authors: Timothy N J
authors: 0000-0001-6141-3261
authors: TN
authors: Bullock
authors: Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine, Charlottesville, VA 22908; mgbrown@virginia.edu.|Beirne B. Carter Center for Immunology Research, University of Virginia School of Medicine, Charlottesville, VA 22908.|Division of Nephrology, Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA 22908.
authors: Michael G
authors: 0000-0003-2872-7685
authors: MG
authors: Brown
mesh_terms: D000208:Acute Disease; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D006566:Herpesviridae Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D018146:Muromegalovirus / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology*
chemical_list: D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7