title: Type I interferons protect T cells against NK cell attack mediated by the activating receptor NCR1.
abstract: Direct type I interferon (IFN) signaling on T cells is necessary for the proper expansion, differentiation, and survival of responding T cells following infection with viruses prominently inducing type I IFN. The reasons for the abortive response of T cells lacking the type I IFN receptor (Ifnar1(-/-)) remain unclear. We report here that Ifnar1(-/-) T cells were highly susceptible to natural killer (NK) cell-mediated killing in a perforin-dependent manner. Depletion of NK cells prior to lymphocytic choriomeningitis virus (LCMV) infection completely restored the early expansion of Ifnar1(-/-) T cells. Ifnar1(-/-) T cells had elevated expression of natural cytotoxicity triggering receptor 1 (NCR1) ligands upon infection, rendering them targets for NCR1 mediated NK cell attack. Thus, direct sensing of type I IFNs by T cells protects them from NK cell killing by regulating the expression of NCR1 ligands, thereby revealing a mechanism by which T cells can evade the potent cytotoxic activity of NK cells.
authors.affiliation: Institute of Microbiology, ETH Zürich, 8093 Zurich, Switzerland.
authors.forename: Josh
authors.initials: J
authors.lastname: Crouse
authors.affiliation: Institute of Microbiology, ETH Zürich, 8093 Zurich, Switzerland.
authors.forename: Gregor
authors.initials: G
authors.lastname: Bedenikovic
authors.affiliation: Institute of Microbiology, ETH Zürich, 8093 Zurich, Switzerland.
authors.forename: Melanie
authors.initials: M
authors.lastname: Wiesel
authors.affiliation: Vital-IT, Swiss Institute of Bioinformatics, CHUV, University of Lausanne, 1015 Lausanne, Switzerland.
authors.forename: Mark
authors.initials: M
authors.lastname: Ibberson
authors.affiliation: Vital-IT, Swiss Institute of Bioinformatics, CHUV, University of Lausanne, 1015 Lausanne, Switzerland.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Xenarios
authors.affiliation: Innsbruck Medical University, 6020 Innsbruck, Austria.
authors.forename: Dorothee
authors.initials: D
authors.lastname: Von Laer
authors.affiliation: Institute for Experimental Infection Research, TWINCORE, Center for Experimental and Clinical Infection Research, Helmholtz Centre for Infection Research, Braunschweig, and Hannover Medical School, 30625 Hannover, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Kalinke
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Institut National de la Santé et de la Recherche Médicale, U1104, Marseille, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Vivier
authors.affiliation: Department of Histology and Embryology, Faculty of Medicine, 51000 Rijeka, Croatia.
authors.forename: Stipan
authors.initials: S
authors.lastname: Jonjic
authors.affiliation: Institute of Microbiology, ETH Zürich, 8093 Zurich, Switzerland. Electronic address: oxenius@micro.biol.ethz.ch.
authors.forename: Annette
authors.initials: A
authors.lastname: Oxenius
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000950:Antigens, Ly / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D007113:Immunity, Innate; D007370:Interferon Type I / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008216:Lymphocytic Choriomeningitis / Q000276:immunology* / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000276:immunology*; D054353:Perforin / Q000096:biosynthesis; D053633:Receptor, Interferon alpha-beta / Q000235:genetics*; D018353:Rhabdoviridae Infections / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D018116:Vesiculovirus / Q000235:genetics / Q000276:immunology; D014779:Virus Replication / Q000276:immunology
chemical_list: D000950:Antigens, Ly; C508032:Ifnar1 protein, mouse; D007370:Interferon Type I; D055627:Natural Cytotoxicity Triggering Receptor 1; C118384:Ncr1 protein, mouse; D054353:Perforin; D053633:Receptor, Interferon alpha-beta