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Sestrins induce natural killer function in senescent-like CD8+ T cells.
Pereira, Branca I; De Maeyer, Roel P H; Covre, Luciana P; Nehar-Belaid, Djamel; Lanna, Alessio; Ward, Sophie; Marches, Radu; Chambers, Emma S; Gomes, Daniel C O; Riddell, Natalie E; Maini, Mala K; Teixeira, Vitor H; Janes, Samuel M; Gilroy, Derek W; Larbi, Anis; Mabbott, Neil A; Ucar, Duygu; Kuchel, George A; Henson, Sian M; Strid, Jessica; Lee, Jun H; Banchereau, Jacques; Akbar, Arne N.
Afiliação
  • Pereira BI; Division of Infection and Immunity, University College London, London, UK.
  • De Maeyer RPH; Division of Infection and Immunity, University College London, London, UK.
  • Covre LP; Division of Infection and Immunity, University College London, London, UK.
  • Nehar-Belaid D; Núcleo de Doenças Infecciosas, Universidade Federal do Espírito Santo, Vitória, Brazil.
  • Lanna A; The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
  • Ward S; Division of Infection and Immunity, University College London, London, UK.
  • Marches R; Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Chambers ES; Department of Medicine, Imperial College London, London, UK.
  • Gomes DCO; The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
  • Riddell NE; Division of Infection and Immunity, University College London, London, UK.
  • Maini MK; Núcleo de Doenças Infecciosas, Universidade Federal do Espírito Santo, Vitória, Brazil.
  • Teixeira VH; Division of Infection and Immunity, University College London, London, UK.
  • Janes SM; Faculty of Health & Medical Sciences, University of Surrey, Guildford, UK.
  • Gilroy DW; Division of Infection and Immunity, University College London, London, UK.
  • Larbi A; Lungs for Living Research Centre, UCL Respiratory, University College London, London, UK.
  • Mabbott NA; Lungs for Living Research Centre, UCL Respiratory, University College London, London, UK.
  • Ucar D; Division of Medicine, University College London, London, UK.
  • Kuchel GA; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore, Singapore.
  • Henson SM; Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, UK.
  • Strid J; The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
  • Lee JH; University of Connecticut Center on Aging, University of Connecticut, Farmington, CT, USA.
  • Banchereau J; William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
  • Akbar AN; Department of Medicine, Imperial College London, London, UK.
Nat Immunol ; 21(6): 684-694, 2020 06.
Article em En | MEDLINE | ID: mdl-32231301
ABSTRACT
Aging is associated with remodeling of the immune system to enable the maintenance of life-long immunity. In the CD8+ T cell compartment, aging results in the expansion of highly differentiated cells that exhibit characteristics of cellular senescence. Here we found that CD27-CD28-CD8+ T cells lost the signaling activity of the T cell antigen receptor (TCR) and expressed a protein complex containing the agonistic natural killer (NK) receptor NKG2D and the NK adaptor molecule DAP12, which promoted cytotoxicity against cells that expressed NKG2D ligands. Immunoprecipitation and imaging cytometry indicated that the NKG2D-DAP12 complex was associated with sestrin 2. The genetic inhibition of sestrin 2 resulted in decreased expression of NKG2D and DAP12 and restored TCR signaling in senescent-like CD27-CD28-CD8+ T cells. Therefore, during aging, sestrins induce the reprogramming of non-proliferative senescent-like CD27-CD28-CD8+ T cells to acquire a broad-spectrum, innate-like killing activity.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Limite: Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article
Texto completo
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XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Limite: Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article