{"doi":"10.1002/eji.202451000","title":"Survival and Developmental Progression of Unselected Thymocytes in the Absence of the T‐Cell Adaptor Gads","abstract":"ABSTRACT Thymocyte β‐selection and positive‐selection depend on TCR signaling via the immune adaptors SLP‐76 and LAT. Gads bridges the recruitment of SLP‐76 to LAT, yet is not required for the maturation of single positive (SP) thymocytes. To illuminate this paradox, we performed tamoxifen‐induced ablation of Gads (Gads iKO ), accompanied by the expression of tdTomato, and compared the development of Gads‐expressing (Tom − ) and Gads‐ablated (Tom + ) thymocytes within the same mouse. Gads iKO (Tom + ) thymocytes exhibited impaired β‐ and positive‐selection, yet δ‐selection was not affected. While susceptible to apoptosis ex vivo, the marked accumulation of self‐MHC nonresponding (CD5 − ) Gads iKO DP thymocytes suggested the possibility of impaired death by neglect in situ. Further supporting this notion, Gads iKO CD5 lo DP thymocytes exhibited reduced apoptosis in situ and reduced CD8‐induced apoptosis ex vivo. Most Gads iKO CD4 SP thymocytes were positively selected, yet a distinct population of unselected (CD5 − TCRβ neg/low CCR7 lo CD24 hi ) CD4 SP thymocytes was seen only in the absence of Gads. This unselected population did not include Treg or TCRγδ subsets; rather, it encompassed CD44 lo CD25 + cells, resembling pre‐β‐selection thymocytes. Our results suggest that Gads promotes passage through key TCR‐driven developmental checkpoints while repressing the progression of unselected DN and DP thymocytes.","journal":"European Journal of Immunology","year":2025,"id":562487,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9531,"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":1189293,"name":"Manal Marzouk","orcid":null,"position":1,"is_corresponding":false},{"id":479517,"name":"Enas Hallumi","orcid":"0000-0003-3702-1940","position":2,"is_corresponding":false},{"id":1189294,"name":"Naama Klopstock","orcid":null,"position":3,"is_corresponding":false},{"id":479533,"name":"Deborah Yablonski","orcid":"0000-0003-2979-0440","position":4,"is_corresponding":false},{"id":1189292,"name":"Rose Shalah","orcid":null,"position":0,"is_corresponding":true}],"reference_count":65,"raw_metadata":null,"created_at":"2026-07-19T02:56:05.550545Z","pmid":"39989300","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":[]}