GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE335nnn/GSE335471/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE335471GEOGSEfalseLymph node contraction links sex-biased naive CD8 T cell decline to compromised antigen recognition during middle age [RNA-seq]The numerical abundance of diverse naive CD8 T cell clones is essential to provide broad protection against infection and cancer. Here, we uncover a sex-biased mechanism of immune aging in which an early, male-biased depletion of naive CD8 T cells driven by accelerated, antigen-agnostic differentiation into virtual memory cells is combined with age-related thymic involution that limits naive CD8 T cell replenishment. These mechanisms lead to contraction of lymph nodes and reduced local naive T cell clone availability, limiting antigen recognition capacity. Therapeutic thymus regeneration via androgen ablation repopulates naive CD8 T cells in lymph nodes, which reinvigorates tumor-specific T cell responses and enhances responsiveness to immune checkpoint blockade. These findings reveal the crucial impact of sex and age on naive T cell clone abundance in lymph nodes and suggest strategies to restore immune competence in middle age males.2026/08/20GSE335471GSM9814280GSM9814265GSM9814287GSM9814288GSM9814266GSM9814285GSM9814263GSM9814286GSM9814264GSM9814283GSM9814261GSM9814262GSM9814284GSM9814281GSM9814282GSM9814260GSM9814302GSM9814269GSM9814300GSM9814289GSM9814267GSM9814268GSM9814301GSM9814290GSM9814291GSM9814276GSM9814298GSM9814299GSM9814277GSM9814255GSM9814296GSM9814274GSM9814297GSM9814275GSM9814294GSM9814272GSM9814273GSM9814295GSM9814292GSM9814270GSM9814271GSM9814293GSM9814258GSM9814259GSM9814256GSM9814278GSM9814279GSM981425734290335471Mus musculus