Type I Interferon Protects Antiviral CD8+ T Cells from NK Cell Cytotoxicity

Haifeng C. Xu, Melanie Grusdat, Aleksandra A. Pandyra, Robin Polz, Jun Huang, Piyush Sharma, René Deenen, Karl Köhrer, Ramtin Rahbar, Andreas Diefenbach, Kathrin Gibbert, Max Löhning, Lena Höcker, Zoe Waibler, Dieter Häussinger, Tak W. Mak, Pamela S. Ohashi, Karl S. Lang, Philipp A. Lang*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

180 Citations (Scopus)

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 Tcell immunity through mechanisms, which remain insufficiently studied. Using the murine lymphocytic choriomeningitis virus model system, we show here that IFN-I signaling on Tcells prevented their rapid elimination invivo. Microarray analyses uncovered that IFN-I triggered the expression of selected inhibitory NK-cell-receptor ligands. Consequently, Tcell immunity of IFN-I receptor (IFNAR)-deficient Tcells could be restored by NK cell depletion or in NK-cell-deficient hosts (Nfil3-/-). The elimination of Ifnar1-/- Tcells was dependent on NK-cell-mediated perforin expression. In summary, we identified IFN-I as a key player regulating the protection of Tcells against regulatory NK cell function.

Original languageEnglish
Pages (from-to)949-960
Number of pages12
JournalImmunity
Volume40
Issue number6
DOIs
Publication statusPublished - 19 Jun 2014
Externally publishedYes

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