Oral Presentation 16th Lorne Infection and Immunity 2026

Understanding healthy aging in centenarians and nonagenarian by defining immune signatures of virus-specific CD8+ T cells and innate immunity    (131262)

Tejas Menon 1 , Aira Cabug 1 , Oanh Nguyen 1 , Louise Rowntree 1 , Jennifer Habel 1 , Shihan Li 1 , Isabelle Foo 1 , Theo Mantamadiotis 2 , Suellen Nicholson 2 , Priyanka Chaurasia 3 , Dene Littler 3 , Stephanie Gras 4 , Jamie Rossjohn 3 , Jane Crowe 5 , Katie Flanagan 6 , Jan Schroeder 1 , Fabio Luciani 7 , Lukasz Kedzierski 1 , Carolien van de Sandt 1 , Katherine Kedzierska 1
  1. Department of Microbiology & Immunology, University of Melbourne at Doherty Institute, Parkville, VIC, Australia
  2. VIDRL, Doherty Institute, Melbourne
  3. Monash University , Clayton
  4. La Trobe University, Bundoora
  5. Deepdene Medical Centre, Deepdene
  6. Westmead Hospital, Westmead
  7. University of New South Wales, Kensington

Centenarians and nonagenarians exemplify healthy aging, yet their immunity is understudied. We defined anti-viral immunity in centenarians and nonagenarians in comparison to children, adults and older adults. We investigated transcriptional and protein profiles of anti-viral epitope-specific CD8+ T cells as well as innate immunity in long-lived centenarians and nonagenarians to provide insights into reduced susceptibility to life-threatening viral infections across pandemics and epidemics. We combined 10x scRNAseq, CITE-seq (130 immune-related protein markers) and DNA-barcoded peptide/HLA-I tetramers specific for influenza A and B, SARS-CoV-2, EBV and CMV to define antigen-specific CD8+ T cells from children (5-15yrs), adults (24-39yrs), older adults (68-75yrs) and long-lived individuals (93-102yrs). We established key transcriptomic and protein signatures underpinning virus-specific CD8+ T cells in healthy aging. Our analyses revealed distinct innate features as well as virus-specific CD8+ T cell signatures from children to long-lived individuals, with more differentiated memory CD8+ T cell subsets in centenarians and nonagenarians expressing unique transcriptomic signatures. Distinct age-specific transcriptomic signatures were also observed for epitope-specific CD8+ T cell populations directed towards chronic and acute viruses. We also deciphered in-depth myeloid and NK cell immunity across the human lifespan. Overall, our study identified immune profiles underpinning innate immunity and virus-specific CD8+ T cells across the human lifespan and provides key insights into immune signatures associated with healthy aging that may identify potential therapeutic targets to reduce disease severity.