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 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. © 2014 Elsevier Inc.