title: Type I interferon protects antiviral CD8+ T cells from NK cell cytotoxicity.
abstract: Despite development of new antiviral drugs, viral infections are still a major health problem. The most potent antiviral defense mechanism is the innate production of type I interferon (IFN-I), which not only limits virus replication but also promotes antiviral T cell immunity through mechanisms, which remain insufficiently studied. Using the murine lymphocytic choriomeningitis virus model system, we show here that IFN-I signaling on T cells prevented their rapid elimination in vivo. Microarray analyses uncovered that IFN-I triggered the expression of selected inhibitory NK-cell-receptor ligands. Consequently, T cell immunity of IFN-I receptor (IFNAR)-deficient T cells could be restored by NK cell depletion or in NK-cell-deficient hosts (Nfil3(-/-)). The elimination of Ifnar1(-/-) T cells was dependent on NK-cell-mediated perforin expression. In summary, we identified IFN-I as a key player regulating the protection of T cells against regulatory NK cell function.
authors.affiliation: Department of Gastroenterology, Hepatology, and Infectious Diseases, Heinrich-Heine-University Düsseldorf, Universitätsstrasse 1, 40225 Düsseldorf, Germany; Institute of Immunology, Medical Faculty, University of Duisburg-Essen, Hufelandstrasse 55, Essen 45147, Germany.
authors.forename: Haifeng C
authors.initials: HC
authors.lastname: Xu
authors.affiliation: Department of Gastroenterology, Hepatology, and Infectious Diseases, Heinrich-Heine-University Düsseldorf, Universitätsstrasse 1, 40225 Düsseldorf, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Grusdat
authors.affiliation: Institute of Immunology, Medical Faculty, University of Duisburg-Essen, Hufelandstrasse 55, Essen 45147, Germany.
authors.forename: Aleksandra A
authors.initials: AA
authors.lastname: Pandyra
authors.affiliation: Department of Gastroenterology, Hepatology, and Infectious Diseases, Heinrich-Heine-University Düsseldorf, Universitätsstrasse 1, 40225 Düsseldorf, Germany.
authors.forename: Robin
authors.initials: R
authors.lastname: Polz
authors.affiliation: Department of Gastroenterology, Hepatology, and Infectious Diseases, Heinrich-Heine-University Düsseldorf, Universitätsstrasse 1, 40225 Düsseldorf, Germany.
authors.forename: Jun
authors.initials: J
authors.lastname: Huang
authors.affiliation: Institute of Immunology, Medical Faculty, University of Duisburg-Essen, Hufelandstrasse 55, Essen 45147, Germany.
authors.forename: Piyush
authors.initials: P
authors.lastname: Sharma
authors.affiliation: Biological and Medical Research Center (BMFZ), Cluster of Excellence on Plant Sciences (CEPLAS), Heinrich-Heine-University, Moorenstrasse 5, Düsseldorf D-40225, Germany.
authors.forename: René
authors.initials: R
authors.lastname: Deenen
authors.affiliation: Biological and Medical Research Center (BMFZ), Cluster of Excellence on Plant Sciences (CEPLAS), Heinrich-Heine-University, Moorenstrasse 5, Düsseldorf D-40225, Germany.
authors.forename: Karl
authors.initials: K
authors.lastname: Köhrer
authors.affiliation: Campell Family Institute for Breast Cancer Research, Princess Margaret Cancer Center, University Health Network (UHN), 620 University Avenue, Toronto, Ontario M5G 2C1, Canada.
authors.forename: Ramtin
authors.initials: R
authors.lastname: Rahbar
authors.affiliation: Institute of Medical Microbiology and Hygiene, University of Mainz Medical Center, Obere Zahlbacher Strasse 67, 55131 Mainz, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Diefenbach
authors.affiliation: Institute of Virology, University Hospital of Essen, University of Duisburg-Essen, Essen 45147, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Gibbert
authors.affiliation: Experimental Immunology, Department of Rheumatology and Clinical Immunology, Charité University Medicine Berlin, 10117 Berlin, Germany; German Rheumatism Research Center (DRFZ), a Leibniz Institute, 10117 Berlin, Germany.
authors.forename: Max
authors.initials: M
authors.lastname: Löhning
authors.affiliation: Paul-Ehrlich-Institut, Paul-Ehrlich-Strasse 51-59, 63225 Langen, Germany.
authors.forename: Lena
authors.initials: L
authors.lastname: Höcker
authors.affiliation: Paul-Ehrlich-Institut, Paul-Ehrlich-Strasse 51-59, 63225 Langen, Germany.
authors.forename: Zoe
authors.initials: Z
authors.lastname: Waibler
authors.affiliation: Department of Gastroenterology, Hepatology, and Infectious Diseases, Heinrich-Heine-University Düsseldorf, Universitätsstrasse 1, 40225 Düsseldorf, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Häussinger
authors.affiliation: Campell Family Institute for Breast Cancer Research, Princess Margaret Cancer Center, University Health Network (UHN), 620 University Avenue, Toronto, Ontario M5G 2C1, Canada.
authors.forename: Tak W
authors.initials: TW
authors.lastname: Mak
authors.affiliation: Campell Family Institute for Breast Cancer Research, Princess Margaret Cancer Center, University Health Network (UHN), 620 University Avenue, Toronto, Ontario M5G 2C1, Canada.
authors.forename: Pamela S
authors.initials: PS
authors.lastname: Ohashi
authors.affiliation: Institute of Immunology, Medical Faculty, University of Duisburg-Essen, Hufelandstrasse 55, Essen 45147, Germany.
authors.forename: Karl S
authors.initials: KS
authors.lastname: Lang
authors.affiliation: Department of Gastroenterology, Hepatology, and Infectious Diseases, Heinrich-Heine-University Düsseldorf, Universitätsstrasse 1, 40225 Düsseldorf, Germany. Electronic address: philipp.lang@med.uni-duesseldorf.de.
authors.forename: Philipp A
authors.initials: PA
authors.lastname: Lang
mesh_terms: D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics; 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*; D008216:Lymphocytic Choriomeningitis / Q000276:immunology* / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054353:Perforin / Q000096:biosynthesis; D053633:Receptor, Interferon alpha-beta / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D014779:Virus Replication / Q000276:immunology
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; C508032:Ifnar1 protein, mouse; D007370:Interferon Type I; C497441:Nfil3 protein, mouse; D054353:Perforin; D053633:Receptor, Interferon alpha-beta