2025/02/15 by Lutz Menzel, Maria Zschummel, Meghan J. O’Melia +9 · 1 voice
Immunology and Microbiology · Medicine · #Immune Cell Function and Interaction #Skin Protection and Aging #T-cell and B-cell Immunology
paper · pdf · doi:10.1101/2025.02.11.637693
openalex publication_date 2025/02/15 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
A diverse naive CD8 T cell repertoire is essential to provide broad protection against infection and cancer. Here, we uncover a sex-biased mechanism of immune aging in which male mice exhibit early depletion of naive CD8 T cells through accelerated, antigen-agnostic differentiation into virtual memory cells. This depletion, compounded by androgen-driven thymic atrophy, leads to contraction of lymph nodes and a reduced local naive T cell repertoire, limiting antigen recognition capacity. Therapeutic thymus regeneration via androgen ablation repopulates naive CD8 T cells in lymph nodes and reinvigorates tumor recognition in middle-aged male mice. These findings reveal the crucial impact of sex and age on locoregional naive T cell repertoires in lymph nodes and suggest strategies to restore immune competence in aging males.