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

doi:10.1016/j.immuni.2014.05.004

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 journal › Article › Research › peer-review

190 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 language	English
Pages (from-to)	949-960
Number of pages	12
Journal	Immunity
Volume	40
Issue number	6
DOIs	https://doi.org/10.1016/j.immuni.2014.05.004
Publication status	Published - 19 Jun 2014
Externally published	Yes

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Xu, H. C., Grusdat, M., Pandyra, A. A., Polz, R., Huang, J., Sharma, P., Deenen, R., Köhrer, K., Rahbar, R., Diefenbach, A., Gibbert, K., Löhning, M., Höcker, L., Waibler, Z., Häussinger, D., Mak, T. W., Ohashi, P. S., Lang, K. S., & Lang, P. A. (2014). Type I Interferon Protects Antiviral CD8⁺ T Cells from NK Cell Cytotoxicity. Immunity, 40(6), 949-960. https://doi.org/10.1016/j.immuni.2014.05.004

@article{a1c9f657957745968c79648b2e4b2a55,

title = "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.",

author = "Xu, {Haifeng C.} and Melanie Grusdat and Pandyra, {Aleksandra A.} and Robin Polz and Jun Huang and Piyush Sharma and Ren{\'e} Deenen and Karl K{\"o}hrer and Ramtin Rahbar and Andreas Diefenbach and Kathrin Gibbert and Max L{\"o}hning and Lena H{\"o}cker and Zoe Waibler and Dieter H{\"a}ussinger and Mak, {Tak W.} and Ohashi, {Pamela S.} and Lang, {Karl S.} and Lang, {Philipp A.}",

note = "Funding Information: The authors are grateful for the technical assistance of Eugen B{\"a}cker and Anne Trenkel. This study was supported by the Alexander von Humboldt Foundation (SKA2008 and SKA2010), the German Research Council (SFB974, LA2558/3-1, LA2558/5-1, TRR60, LA1419/5-1, RTG1949), and the NIH Tetramer Facility. Further support came from the Strategic Research Fund and the Forschungskomission of the Heinrich Heine University. ",

year = "2014",

month = jun,

day = "19",

doi = "10.1016/j.immuni.2014.05.004",

language = "English",

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journal = "Immunity",

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Xu, HC, Grusdat, M, Pandyra, AA, Polz, R, Huang, J, Sharma, P, Deenen, R, Köhrer, K, Rahbar, R, Diefenbach, A, Gibbert, K, Löhning, M, Höcker, L, Waibler, Z, Häussinger, D, Mak, TW, Ohashi, PS, Lang, KS & Lang, PA 2014, 'Type I Interferon Protects Antiviral CD8⁺ T Cells from NK Cell Cytotoxicity', Immunity, vol. 40, no. 6, pp. 949-960. https://doi.org/10.1016/j.immuni.2014.05.004

TY - JOUR

T1 - Type I Interferon Protects Antiviral CD8+ T Cells from NK Cell Cytotoxicity

AU - Xu, Haifeng C.

AU - Grusdat, Melanie

AU - Pandyra, Aleksandra A.

AU - Polz, Robin

AU - Huang, Jun

AU - Sharma, Piyush

AU - Deenen, René

AU - Köhrer, Karl

AU - Rahbar, Ramtin

AU - Diefenbach, Andreas

AU - Gibbert, Kathrin

AU - Löhning, Max

AU - Höcker, Lena

AU - Waibler, Zoe

AU - Häussinger, Dieter

AU - Mak, Tak W.

AU - Ohashi, Pamela S.

AU - Lang, Karl S.

AU - Lang, Philipp A.

N1 - Funding Information: The authors are grateful for the technical assistance of Eugen Bäcker and Anne Trenkel. This study was supported by the Alexander von Humboldt Foundation (SKA2008 and SKA2010), the German Research Council (SFB974, LA2558/3-1, LA2558/5-1, TRR60, LA1419/5-1, RTG1949), and the NIH Tetramer Facility. Further support came from the Strategic Research Fund and the Forschungskomission of the Heinrich Heine University.

PY - 2014/6/19

Y1 - 2014/6/19

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84902651736&partnerID=8YFLogxK

U2 - 10.1016/j.immuni.2014.05.004

DO - 10.1016/j.immuni.2014.05.004

M3 - Article

C2 - 24909887

AN - SCOPUS:84902651736

SN - 1074-7613

VL - 40

SP - 949

EP - 960

JO - Immunity

JF - Immunity

IS - 6

ER -

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

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