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RESEARCH PRODUCT
A central role for Notch in effector CD8(+) T cell differentiation.
Stella E. Van TrierumBrian J. LaidlawA. Marcel WillemsenAnja Ten BrinkeAntoine H. C. Van KampenChristina HelbigRebecca GentekDerk AmsenJ. Magarian BlanderRuud Van BeekGuus F. RimmelzwaanRonald A. BackerRonald A. BackerYevan S De SouzaAndrew KentSusan M. KaechKlaas P. J. M. Van GisbergenClaudia X. Dominguezsubject
ImmunologyNotch signaling pathwayMice TransgenicCell SeparationBiologyAdaptive ImmunityCD8-Positive T-LymphocytesEffector cellLymphocyte ActivationReal-Time Polymerase Chain ReactionArticlememoryMiceOrthomyxoviridae InfectionsCell surface receptorT-Lymphocyte SubsetsTransduction GeneticPrecursor cellImmunology and AllergyCytotoxic T cellAnimalsGeneticsReceptors NotchEffectorCell DifferentiationFlow CytometryAdoptive TransferTEC3. Good healthCell biologyMice Inbred C57BLeffectorCD8 T cellMPCInfluenza A virusinflammationTranscriptomeCD8description
Activated CD8(+) T cells choose between terminal effector cell (TEC) or memory precursor cell (MPC) fates. We found that the signaling receptor Notch controls this 'choice'. Notch promoted the differentiation of immediately protective TECs and was correspondingly required for the clearance of acute infection with influenza virus. Notch activated a major portion of the TEC-specific gene-expression program and suppressed the MPC-specific program. Expression of Notch was induced on naive CD8(+) T cells by inflammatory mediators and interleukin 2 (IL-2) via pathways dependent on the metabolic checkpoint kinase mTOR and the transcription factor T-bet. These pathways were subsequently amplified downstream of Notch, creating a positive feedback loop. Notch thus functions as a central hub where information from different sources converges to match effector T cell differentiation to the demands of an infection.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2014-01-01 | Nature immunology |