Immunity
Volume 40, Issue 6, 19 June 2014, Pages 949-960
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Article
Type I Interferon Protects Antiviral CD8+ T Cells from NK Cell Cytotoxicity

https://doi.org/10.1016/j.immuni.2014.05.004Get rights and content
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Highlights

  • Ifnar1–/– T cells proliferate in vitro, but not in vivo, suggesting cell interaction

  • Microarray analyses identify MHC molecules as being regulated by type I interferons

  • NK cell deficiency rescues expansion and function of IFN-I unresponsive T cells

  • NK-cell-mediated killing of activated Ifnar1–/– CD8+ T cells depends on perforin

Summary

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.

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