{"doi":"10.1101/2025.02.01.636039","title":"Transcriptional control of T cell tissue adaptation and effector function in infants and adults","abstract":"ABSTRACT The first years of life are essential for the development of memory T cells, which rapidly populate the body’s diverse tissue sites during infancy. However, the degree to which tissue memory T cell responses in early life reflect those during adulthood is unclear. Here, we use single cell RNA-sequencing of resting and ex vivo activated T cells from lymphoid and mucosal tissues of infant (aged 2-9 months) and adult (aged 40-65 years) human organ donors to dissect the transcriptional programming of memory T cells over age. Infant memory T cells demonstrate a unique stem-like transcriptional profile and tissue adaptation program, yet exhibit reduced activation capacity and effector function relative to adults. Using CRISPR-Cas9 knockdown, we define Helios ( IKZF2 ) as a critical transcriptional regulator of the infant-specific tissue adaptation program and restricted effector state. Our findings reveal key transcriptional mechanisms that control tissue T cell fate and function in early life.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":555991,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9308,"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":558051,"name":"Hanna Mendes Levitin","orcid":null,"position":1,"is_corresponding":false},{"id":225921,"name":"Thomas J. Connors","orcid":"0000-0002-0199-7733","position":2,"is_corresponding":false},{"id":838851,"name":"David Chen","orcid":"0000-0002-9710-1857","position":3,"is_corresponding":false},{"id":865594,"name":"Jenny Jin","orcid":"0009-0000-8503-9761","position":4,"is_corresponding":false},{"id":700830,"name":"Puspa Thapa","orcid":"0000-0001-6769-2441","position":5,"is_corresponding":false},{"id":700831,"name":"Rebecca Guyer","orcid":"0000-0003-3777-2197","position":6,"is_corresponding":false},{"id":850951,"name":"Daniel P. Caron","orcid":"0000-0002-1500-8713","position":7,"is_corresponding":false},{"id":225928,"name":"Joshua I. Gray","orcid":"0000-0003-2796-5470","position":8,"is_corresponding":false},{"id":229312,"name":"Rei Matsumoto","orcid":null,"position":9,"is_corresponding":false},{"id":621509,"name":"Masaru Kubota","orcid":"0000-0002-4095-738X","position":10,"is_corresponding":false},{"id":356517,"name":"Maigan A. Brusko","orcid":"0000-0002-4331-2202","position":11,"is_corresponding":false},{"id":356521,"name":"Todd M. Brusko","orcid":"0000-0003-2878-9296","position":12,"is_corresponding":false},{"id":225941,"name":"Donna L. Färber","orcid":"0000-0001-8236-9183","position":13,"is_corresponding":false},{"id":225061,"name":"Peter A. Sims","orcid":"0000-0002-3921-4837","position":14,"is_corresponding":false},{"id":225925,"name":"Peter A. Szabo","orcid":"0000-0003-1603-761X","position":0,"is_corresponding":true}],"reference_count":70,"raw_metadata":null,"created_at":"2026-07-19T02:55:03.976486Z","pmid":"39974963","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":[]}