Central memory T cells with key TCR repertoires and gene expression profiles dominate influenza CD8+T cell pools across the human lifespan

• 成果类型: Article
• 署名作者: Menon, Tejas; McQuilten, Hayley A.; Samir, Jerome; Nguyen, Thi H. O.; Lim, Ratana; Kaur, Jasveen; Rizzetto, Simone; Eltahla, Auda; Thomas, Paul G.; Lappas, Martha; Rossjohn, Jamie; Gras, Stephanie; Crowe, Jane; Flanagan, Katie L.; Luciani, Fabio; Doherty, Peter C.; van de Sandt, Carolien E.; Kedzierska, Katherine
• 署名单位: University of Melbourne; Peter Doherty Institute; University of New South Wales Sydney; University of Melbourne; University of Tasmania; University of Tasmania; St Jude Children's Research Hospital; Monash University; Monash University; Cardiff University; La Trobe University; Royal Melbourne Institute of Technology (RMIT); Clifford Craig Foundation; Launceston General Hospital
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-15243
• DOI: 10.1073/pnas.2501167122
• 发表日期: 2025-07-29
• 关键词: subsets; immunity; HEALTH; differentiation; initiation; diversity; division

摘要

Central memory CD8+T cells (Tcm) represent the prominent memory T cell subset in human blood, yet the persistence of T cell receptor (TCR) clonotypic and transcriptional features of epitope-specific Tcm pools across the human lifespan remains unknown. We analyzed Tcm CD8+ T cells specific for HLA-A*02:01-M158-66 (A2/M158; a prominent influenza epitope) in newborns, children, adults, and older adults directly ex vivo. Our data provide evidence that epitope-specific Tcm CD8+ pools dominate influenza-specific memory A2/M158+CD8+ T cell responses from the early childhood until old age. Tcm gene signatures were largely maintained across the age groups, although self-renewal genes defined Tcm pools in children, while older adult Tcm A2/M158+CD8+ T cells displayed detoxication and stress profiles. TCR alpha beta diversity within Tcm A2/M158+CD8+ T cell pools was greater in children and older adults, when compared to adults. The key public-associated TCR alpha beta clonotypes largely persisted across the human lifespan, although their highest frequency was detected in adults, reflecting lower TCR alpha beta diversity in this group. Older adults displayed increased TCR alpha beta heterogeneity, underpinned by large TCR alpha beta clonotype expansions of private TCR alpha beta clonotypes. Our study highlights the importance of largely preserved virus-specific Tcm pools across the human lifespan and advocates for boosting persistent TCR alpha beta clonotypes within this key peripheral blood subset.