Your browser doesn't support javascript.
loading
Newborn and child-like molecular signatures in older adults stem from TCR shifts across human lifespan.
van de Sandt, Carolien E; Nguyen, Thi H O; Gherardin, Nicholas A; Crawford, Jeremy Chase; Samir, Jerome; Minervina, Anastasia A; Pogorelyy, Mikhail V; Rizzetto, Simone; Szeto, Christopher; Kaur, Jasveen; Ranson, Nicole; Sonda, Sabrina; Harper, Alice; Redmond, Samuel J; McQuilten, Hayley A; Menon, Tejas; Sant, Sneha; Jia, Xiaoxiao; Pedrina, Kate; Karapanagiotidis, Theo; Cain, Natalie; Nicholson, Suellen; Chen, Zhenjun; Lim, Ratana; Clemens, E Bridie; Eltahla, Auda; La Gruta, Nicole L; Crowe, Jane; Lappas, Martha; Rossjohn, Jamie; Godfrey, Dale I; Thomas, Paul G; Gras, Stephanie; Flanagan, Katie L; Luciani, Fabio; Kedzierska, Katherine.
  • van de Sandt CE; Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
  • Nguyen THO; Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
  • Gherardin NA; Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
  • Crawford JC; Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
  • Samir J; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, USA.
  • Minervina AA; School of Medical Sciences and The Kirby Institute, UNSW Sydney, Sydney, New South Wales, Australia.
  • Pogorelyy MV; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, USA.
  • Rizzetto S; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, USA.
  • Szeto C; School of Medical Sciences and The Kirby Institute, UNSW Sydney, Sydney, New South Wales, Australia.
  • Kaur J; Viral and Structural Immunology Laboratory, Department of Biochemistry and Chemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Victoria, Australia.
  • Ranson N; Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.
  • Sonda S; School of Health Sciences and School of Medicine, University of Tasmania, Launceston, Tasmania, Australia.
  • Harper A; School of Health Sciences and School of Medicine, University of Tasmania, Launceston, Tasmania, Australia.
  • Redmond SJ; School of Health Sciences and School of Medicine, University of Tasmania, Launceston, Tasmania, Australia.
  • McQuilten HA; School of Health Sciences and School of Medicine, University of Tasmania, Launceston, Tasmania, Australia.
  • Menon T; Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
  • Sant S; Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
  • Jia X; Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
  • Pedrina K; Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
  • Karapanagiotidis T; Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
  • Cain N; Victorian Infectious Diseases Reference Laboratory, The Royal Melbourne Hospital at The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
  • Nicholson S; Victorian Infectious Diseases Reference Laboratory, The Royal Melbourne Hospital at The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
  • Chen Z; Victorian Infectious Diseases Reference Laboratory, The Royal Melbourne Hospital at The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
  • Lim R; Victorian Infectious Diseases Reference Laboratory, The Royal Melbourne Hospital at The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
  • Clemens EB; Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
  • Eltahla A; Obstetrics, Nutrition and Endocrinology Group, Department of Obstetrics and Gynaecology, University of Melbourne, Melbourne, Victoria, Australia.
  • La Gruta NL; Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
  • Crowe J; School of Medical Sciences and The Kirby Institute, UNSW Sydney, Sydney, New South Wales, Australia.
  • Lappas M; Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.
  • Rossjohn J; Deepdene Surgery, Deepdene, Victoria, Australia.
  • Godfrey DI; Obstetrics, Nutrition and Endocrinology Group, Department of Obstetrics and Gynaecology, University of Melbourne, Melbourne, Victoria, Australia.
  • Thomas PG; Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.
  • Gras S; Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff, UK.
  • Flanagan KL; Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
  • Luciani F; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, USA.
  • Kedzierska K; Viral and Structural Immunology Laboratory, Department of Biochemistry and Chemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Victoria, Australia.
Nat Immunol ; 24(11): 1890-1907, 2023 Nov.
Article en En | MEDLINE | ID: mdl-37749325
ABSTRACT
CD8+ T cells provide robust antiviral immunity, but how epitope-specific T cells evolve across the human lifespan is unclear. Here we defined CD8+ T cell immunity directed at the prominent influenza epitope HLA-A*0201-M158-66 (A2/M158) across four age groups at phenotypic, transcriptomic, clonal and functional levels. We identify a linear differentiation trajectory from newborns to children then adults, followed by divergence and a clonal reset in older adults. Gene profiles in older adults closely resemble those of newborns and children, despite being clonally distinct. Only child-derived and adult-derived A2/M158+CD8+ T cells had the potential to differentiate into highly cytotoxic epitope-specific CD8+ T cells, which was linked to highly functional public T cell receptor (TCR)αß signatures. Suboptimal TCRαß signatures in older adults led to less proliferation, polyfunctionality, avidity and recognition of peptide mutants, although displayed no signs of exhaustion. These data suggest that priming T cells at different stages of life might greatly affect CD8+ T cell responses toward viral infections.
Asunto(s)
Texto completo
Imprimir
XML
PubMed Links
Search on Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Linfocitos T CD8-positivos / Longevidad Límite: Aged / Humans / Newborn Idioma: En Año: 2023 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Search on Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Linfocitos T CD8-positivos / Longevidad Límite: Aged / Humans / Newborn Idioma: En Año: 2023 Tipo del documento: Article