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Type I Interferons Protect T Cells against NK Cell Attack Mediated by the Activating Receptor NCR1

Crouse, J and Bedenikovic, G and Wiesel, M and Ibberson, M and Xenarios, I and VonLaer, D and Kalinke, U and Vivier, E and Jonjic, S and Oxenius, A (2014) Type I Interferons Protect T Cells against NK Cell Attack Mediated by the Activating Receptor NCR1. Immunity. pp. 961-973.

Abstract

Direct type I interferon (IFN) signaling on Tcells is necessary for the proper expansion, differentiation, and survival of responding Tcells following infection with viruses prominently inducing type I IFN. The reasons for the abortive response of Tcells lacking the type I IFN receptor (Ifnar1<sup>-/-</sup>) remain unclear. We report here that Ifnar1<sup>-/-</sup> Tcells 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<sup>-/-</sup> Tcells. Ifnar1<sup>-/-</sup> Tcells 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 Tcells protects them from NK cell killing by regulating the expression of NCR1 ligands, thereby revealing a mechanism by which Tcells can evade the potent cytotoxic activity of NK cells. 2014 Elsevier Inc

Item Type: Article
Additional Information: NIBR author: Wiesel, M institute: NIBR- address only contributor address: (Crouse, Bedenikovic, Wiesel, Oxenius) Institute of Microbiology, ETH Zurich, 8093 Zurich, Switzerland (Ibberson, Xenarios) Vital-IT, Swiss Institute of Bioinformatics, CHUV, University of Lausanne, 1015 Lausanne, Switzerland (VonLaer) Innsbruck Medical University, 6020 Innsbruck, Austria (Kalinke) 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 (Vivier) Centre d'Immunologie de Marseille-Luminy, Institut National de la Sante et de la Recherche Medicale, U1104, Marseille, France (Jonjic) Department of Histology and Embryology, Faculty of Medicine, 51000 Rijeka, Croatia (Wiesel) Novartis Institutes for Biomedical Research, 4033 Basel, Switzerland
Date Deposited: 13 Oct 2015 13:12
Last Modified: 13 Oct 2015 13:12
URI: https://oak.novartis.com/id/eprint/22755

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