title: NKG2D stimulation of CD8+T cells during priming promotes their capacity to produce cytokines in response to viral infection in mice.
abstract: Natural killer group 2 member D (NKG2D) is an activating receptor that is expressed on most cytotoxic cells of the immune system, including NK cells, γδ, and CD8+T cells. It is still a matter of debate whether and how NKG2D mediates priming of CD8+T cells in vivo, due to a lack of studies where NKG2D is eliminated exclusively in these cells. Here, we studied the impact of NKG2D on effector CD8+T-cell formation. NKG2D deficiency that is restricted to murine CD8+T cells did not impair antigen-specific T-cell expansion following mouse CMV and lymphocytic choriomeningitis virus infection, but reduced their capacity to produce cytokines. Upon infection, conventional dendritic cells induce NKG2D ligands, which drive cytokine production on CD8+T cells via the Dap10 signaling pathway. T-cell development, homing, and proliferation were not affected by NKG2D deficiency and cytotoxicity was only impaired when strong T-cell receptor (TCR) stimuli were used. Transfer of antigen-specific CD8+T cells demonstrated that NKG2D deficiency attenuated their capacity to reduce viral loads. The inability of NKG2D-deficient cells to produce cytokines could be overcome with injection of IL-15 superagonist during priming. In summary, our data show that NKG2D has a nonredundant role in priming of CD8+T cells to produce antiviral cytokines.
authors.affiliation: Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.
authors.forename: Inga
authors.initials: I
authors.lastname: Kavazović
authors.affiliation: Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.
authors.forename: Maja
authors.initials: M
authors.lastname: Lenartić
authors.affiliation: Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.
authors.forename: Vedrana
authors.initials: V
authors.lastname: Jelenčić
authors.affiliation: Department of Medical Physics, University Hospital Rijeka, Rijeka, Croatia.
authors.forename: Slaven
authors.initials: S
authors.lastname: Jurković
authors.affiliation: Institute for Virology,, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
authors.forename: Niels A W
authors.initials: NAW
authors.lastname: Lemmermann
authors.affiliation: Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.
authors.forename: Stipan
authors.identifier: 0000-0001-5003-3108
authors.initials: S
authors.lastname: Jonjić
authors.affiliation: Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.
authors.forename: Bojan
authors.identifier: 0000-0003-3930-9630
authors.initials: B
authors.lastname: Polić
authors.affiliation: Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.|Department of Experimental Immunology, Amsterdam Medical Center, Amsterdam, The Netherlands.
authors.forename: Felix M
authors.identifier: 0000-0002-1333-8882
authors.initials: FM
authors.lastname: Wensveen
mesh_terms: D000818:Animals; D001117:Arenaviridae Infections / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology; D006566:Herpesviridae Infections / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D018146:Muromegalovirus; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D016207:Cytokines; C492355:Hcst protein, mouse; C527086:Klrk1 protein, mouse; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic
keywords: CD8+ T cells; Costimulation; Cytokines; NKG2D; Priming; mCMV