Defining molecular gene profiles that underpin superior virus-specific CD8+ T cell immunity in nonagenarian and centenarians 3494
Abstract Description Centenarians and nonagenarians exemplify healthy aging, yet it is unknown whether longevity is linked to optimal anti-viral immunity. We defined anti-viral immunity in centenarians and nonagenarians and compared to children, adults and older adults to understand transcriptional profiles of epitope-specific CD8+ T cells in long-lived nonagenarians and centenarians to gain insight on their reduced susceptibility to life-threatening viral infections. We performed scRNAseq and measured the cell-surface proteome of CD8+ T cells specific for peptide/HLA-I tetramers for influenza A and B, SARS-CoV-2, EBV and CMV to define epitope-specific CD8+ T cells from children (5-15y), adults (24-39y), older adults (68-75y) and long-lived individuals (93-102y) to establish their key transcriptomic and protein signatures. Our analyses of virus-specific CD8+ T cell trajectory across age groups revealed more differentiated memory CD8+ T cell subsets in centenarians and nonagenarians that had unique transcriptomic signatures. Strikingly, 90+ year olds displayed differential clustering of terminally differentiated CD8+ T cells. Unique age-specific signatures were also observed for epitope-specific CD8+ T cell populations in both chronic and acute viruses. We identified immune profiles for virus-specific CD8+ T cells across the human lifespan and provide key insights into biomarkers associated with healthy immune aging that may identify potential therapeutic targets to reduce disease severity. Funding Sources National Health and Medical Research Council (NHMRC), Australian Research Council (ARC). Topic Categories Lymphocyte Differentiation and Peripheral Maintenance (LYM)
Authors
- Tejas Menon (ORCID: https://orcid.org/0000-0001-7636-0051)
- Stefan Schattgen (ORCID: https://orcid.org/0000-0002-6860-5079)
- Fabio Luciani (ORCID: https://orcid.org/0000-0003-0666-6324)
- Malet Aban
- Paul Glyndwr Thomas (ORCID: https://orcid.org/0000-0001-7955-0256)
- Katherine Kedzierska (ORCID: https://orcid.org/0000-0001-6141-335X)
- Jennifer R. Habel (ORCID: https://orcid.org/0000-0003-0380-1527)
- Celia Douros
- Priyanka Chaurasia (ORCID: https://orcid.org/0000-0002-3755-159X)
- Łukasz Kedzierski (ORCID: https://orcid.org/0000-0003-0203-1057)
- Heidi Peck (ORCID: https://orcid.org/0000-0002-3651-2839)
- Isabelle J. H. Foo (ORCID: https://orcid.org/0000-0002-4465-7245)
- Katie L. Flanagan (ORCID: https://orcid.org/0000-0002-1575-1953)
- Louise C. Rowntree (ORCID: https://orcid.org/0000-0002-0649-5089)
- Suellen R Nicholson (ORCID: https://orcid.org/0000-0001-6585-7150)
- Oanh Nguyen
- Dene R. Littler (ORCID: https://orcid.org/0000-0001-5904-1905)
- Ian Barr (ORCID: https://orcid.org/0000-0002-7351-418X)
- Carolien E. van de Sandt (ORCID: https://orcid.org/0000-0002-4155-7433)
- Jamie Rossjohn (ORCID: https://orcid.org/0000-0002-2020-7522)
- Jan Schroeder (ORCID: https://orcid.org/0000-0001-5270-0605)
- Stéphanie Gras (ORCID: https://orcid.org/0000-0001-7416-038X)
- Theo Karapanagiotidis (ORCID: https://orcid.org/0000-0001-7057-9765)
- Shihan Li (ORCID: https://orcid.org/0000-0003-3207-7064)
- Jane Crowe
Institutions
- St. Jude Children's Research Hospital (US)
- The Royal Melbourne Hospital (AU)
- The University of Melbourne (AU)
- La Trobe University (AU)
- UNSW Sydney (AU)
- Victorian Infectious Diseases Reference Laboratory (AU)
- Peter Doherty Institute (AU)
- RMIT Europe (ES)
- Monash University (AU)
Publication Details
- Journal
- The Journal of Immunology
- Published
- 2025-11-01
- DOI
- https://doi.org/10.1093/jimmun/vkaf283.1290
- Primary Topic
- Genetics, Aging, and Longevity in Model Organisms
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Deutsche Forschungsgemeinschaft
- Bundesministerium für Bildung und Forschung