0000000000173872

AUTHOR

Derk Amsen

showing 3 related works from this author

A central role for Notch in effector CD8(+) T cell differentiation.

2014

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 d…

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 virusinflammationTranscriptomeCD8Nature immunology
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Notch in T Cell Differentiation: All Things Considered.

2015

Differentiation of naive T cells into effector cells is required for optimal protection against different classes of microbial pathogen and for the development of immune memory. Recent findings have revealed important roles for the Notch signaling pathway in T cell differentiation into all known effector subsets, raising the question of how this pathway controls such diverse differentiation programs. Studies in preclinical models support the therapeutic potential of manipulating the Notch pathway to alleviate immune pathology, highlighting the importance of understanding the mechanisms through which Notch regulates T cell differentiation and function. We review these findings here, and outl…

Cell typeReceptors NotchEffectorT cellT-LymphocytesImmunologyNotch signaling pathwayCell DifferentiationBiologyLymphocyte ActivationImmune systemmedicine.anatomical_structureT cell differentiationImmunologymedicineImmunology and AllergyAnimalsHumansReceptorFunction (biology)Signal TransductionTrends in immunology
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The Fate Choice Between Effector and Memory T Cell Lineages: Asymmetry, Signal Integration, and Feedback to Create Bistability

2018

Abstract CD8+ T cells clear primary infections with intracellular pathogens and provide long-term immunity against reinfection. Two different types of CD8+ T cells are responsible for these functions: short-lived effector T cells and memory T cells. The cellular relationship between these two types of CD8+ T cells has been subject to much investigation. Both cell types can derive from a single naive CD8+ T cell precursor. Their generation requires a fate choice early during a T cell response. As a result, two populations of T cells emerge. One of these consists of terminally differentiated short-lived effector T cells. The other contains cells able to develop into long-lived memory T cells.…

0301 basic medicineCell typeCell divisionNaive T cellT cellNotch signaling pathwayBiologyCell biology03 medical and health sciences030104 developmental biologymedicine.anatomical_structureAsymmetric cell divisionmedicineMemory T cellCD8
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