GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE344nnn/GSE344576/primaryOK200OtherMus musculusOtherhttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE344576GEOGSEfalseLymph node contraction links sex-biased naive CD8 T cell decline to compromised antigen recognition during middle age [TCR-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.2026/08/21GSE344576GSM9981633GSM9981622GSM9981623GSM9981634GSM9981635GSM9981624GSM9981625GSM9981630GSM9981631GSM9981620GSM9981621GSM9981632GSM9981619GSM9981626GSM9981616GSM9981627GSM9981628GSM9981617GSM9981618GSM998162934290344576Mus musculus