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Immunity. 2014 Jun 19;40(6):949-60. doi: 10.1016/j.immuni.2014.05.004. Epub 2014 Jun 5.

Type I interferon protects antiviral CD8+ T cells from NK cell cytotoxicity.

Author information

1
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.
2
Department of Gastroenterology, Hepatology, and Infectious Diseases, Heinrich-Heine-University Düsseldorf, Universitätsstrasse 1, 40225 Düsseldorf, Germany.
3
Institute of Immunology, Medical Faculty, University of Duisburg-Essen, Hufelandstrasse 55, Essen 45147, Germany.
4
Biological and Medical Research Center (BMFZ), Cluster of Excellence on Plant Sciences (CEPLAS), Heinrich-Heine-University, Moorenstrasse 5, Düsseldorf D-40225, Germany.
5
Campell Family Institute for Breast Cancer Research, Princess Margaret Cancer Center, University Health Network (UHN), 620 University Avenue, Toronto, Ontario M5G 2C1, Canada.
6
Institute of Medical Microbiology and Hygiene, University of Mainz Medical Center, Obere Zahlbacher Strasse 67, 55131 Mainz, Germany.
7
Institute of Virology, University Hospital of Essen, University of Duisburg-Essen, Essen 45147, Germany.
8
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.
9
Paul-Ehrlich-Institut, Paul-Ehrlich-Strasse 51-59, 63225 Langen, Germany.
10
Department of Gastroenterology, Hepatology, and Infectious Diseases, Heinrich-Heine-University Düsseldorf, Universitätsstrasse 1, 40225 Düsseldorf, Germany. Electronic address: philipp.lang@med.uni-duesseldorf.de.

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.

PMID:
24909887
DOI:
10.1016/j.immuni.2014.05.004
[Indexed for MEDLINE]
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