6533b836fe1ef96bd12a1532

RESEARCH PRODUCT

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

Dieter HäussingerLena HöckerKarl S. LangAndreas DiefenbachMelanie GrusdatHaifeng C. XuHaifeng C. XuAleksandra A. PandyraPiyush SharmaRamtin RahbarPamela S. OhashiRené DeenenKathrin GibbertTak W. MakRobin PolzMax LöhningMax LöhningZoe WaiblerPhilipp A. LangKarl KöhrerJun Huang

subject

Cytotoxicity ImmunologicImmunologyMedizinReceptor Interferon alpha-betaCD8-Positive T-LymphocytesLymphocytic ChoriomeningitisVirus ReplicationLymphocytic choriomeningitisVirusMiceImmunityInterferonmedicineAnimalsLymphocytic choriomeningitis virusImmunology and AllergyCytotoxic T cellCells CulturedMice KnockoutbiologyPerforinNFIL3medicine.diseaseVirologyImmunity InnateKiller Cells NaturalMice Inbred C57BLBasic-Leucine Zipper Transcription FactorsInfectious DiseasesViral replicationPerforinInterferon Type IImmunologybiology.proteinSignal Transductionmedicine.drug

description

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.

yearjournalcountryeditionlanguage
2014-06-01Immunity
10.1016/j.immuni.2014.05.004http://dx.doi.org/10.1016/j.immuni.2014.05.004