[HTML][HTML] Type I interferon protects antiviral CD8+ T cells from NK cell cytotoxicity

HC Xu, M Grusdat, AA Pandyra, R Polz, J Huang… - Immunity, 2014 - cell.com
HC Xu, M Grusdat, AA Pandyra, R Polz, J Huang, P Sharma, R Deenen, K Köhrer, R Rahbar…
Immunity, 2014cell.com
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 …
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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