Lutz Menzel, Maria Zschummel, Meghan J O'Melia, Marten Sandstedt, Hengbo Zhou, Pin-Ji Lei, Lingshan Liu, Hang Lee, Debattama R Sen, Lance L Munn, Lena Jonasson, Timothy P Padera
{"title":"Lymph node contraction links sex-biased naive CD8 T cell decline to compromised antigen recognition.","authors":"Lutz Menzel, Maria Zschummel, Meghan J O'Melia, Marten Sandstedt, Hengbo Zhou, Pin-Ji Lei, Lingshan Liu, Hang Lee, Debattama R Sen, Lance L Munn, Lena Jonasson, Timothy P Padera","doi":"10.1101/2025.02.11.637693","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844512/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"bioRxiv : the preprint server for biology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1101/2025.02.11.637693","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
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.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
