ArticlebioRxiv : the preprint server for biology2025
Lymph node contraction links sex-biased naive CD8 T cell decline to compromised antigen recognition.
Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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12 authors.
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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.
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