{"doi":"10.1101/2025.02.11.637693","title":"Lymph node contraction links sex-biased naive CD8 T cell decline to compromised antigen recognition during middle age","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.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":557330,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9498,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1201498,"name":"Maria Zschummel","orcid":"0000-0002-4778-8742","position":1,"is_corresponding":false},{"id":240994,"name":"Meghan J. O’Melia","orcid":"0000-0003-2223-1849","position":2,"is_corresponding":false},{"id":653570,"name":"Mårten Sandstedt","orcid":"0000-0002-0973-9499","position":3,"is_corresponding":false},{"id":288134,"name":"Hengbo Zhou","orcid":"0000-0002-9948-7909","position":4,"is_corresponding":false},{"id":628137,"name":"Pin‐Ji Lei","orcid":"0000-0003-2539-5179","position":5,"is_corresponding":false},{"id":1457299,"name":"Lingshan Liu","orcid":"0009-0008-4422-2445","position":6,"is_corresponding":false},{"id":270867,"name":"Hang Lee","orcid":"0000-0002-3498-236X","position":7,"is_corresponding":false},{"id":16000,"name":"Debattama R. Sen","orcid":"0000-0002-0947-8284","position":8,"is_corresponding":false},{"id":108323,"name":"Lance L. Munn","orcid":"0000-0003-0698-7232","position":9,"is_corresponding":false},{"id":1457577,"name":"Lena Jonasson","orcid":null,"position":10,"is_corresponding":false},{"id":444976,"name":"Timothy P. Padera","orcid":"0000-0002-3453-9384","position":11,"is_corresponding":false},{"id":1025654,"name":"Lutz Menzel","orcid":"0000-0002-3816-6255","position":0,"is_corresponding":true}],"reference_count":78,"raw_metadata":null,"created_at":"2026-07-19T02:55:17.435961Z","pmid":"39990447","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}