{"doi":"10.1038/s42003-024-06456-3","title":"Interconnected lineage trajectories link conventional and natural killer (NK)-like exhausted CD8+ T cells beneficial in type 1 diabetes","abstract":"Abstract Distinct Natural Killer (NK)-like CD57 + and PD-1 + CD8 + exhausted-like T cell populations (Tex) have both been linked to beneficial immunotherapy response in autoimmune type 1 diabetes (T1D) patients. The origins and relationships between these cell types are poorly understood. Here we show that while PD-1 + and CD57 + Tex populations are epigenetically similar, CD57 + Tex cells display unique increased chromatin accessibility of inhibitory Killer Cell Immunoglobulin-like Receptor (iKIR) and other NK cell genes. PD-1 + and CD57 + Tex also show reciprocal expression of Inhibitory Receptors (IRs) and iKIRs accompanied by chromatin accessibility of Tcf1 and Tbet transcription factor target sites, respectively. CD57 + Tex show unappreciated gene expression heterogeneity and share clonal relationships with PD-1 + Tex, with these cells differentiating along four interconnected lineage trajectories: Tex-PD-1 + , Tex-CD57 + , Tex-Branching, and Tex-Fluid. Our findings demonstrate new relationships between Tex-like populations in human autoimmune disease and suggest that modulating common precursor populations may enhance response to autoimmune disease treatment.","journal":"Communications Biology","year":2024,"id":447021,"datarank":0.29188652235829704,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.0,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9432,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":308285,"name":"Kirsten E. Diggins","orcid":"0000-0003-1622-0158","position":1,"is_corresponding":false},{"id":328022,"name":"Alice Wiedeman","orcid":"0000-0001-7329-7288","position":2,"is_corresponding":false},{"id":1173367,"name":"Elisavet Serti","orcid":"0000-0003-4129-0254","position":3,"is_corresponding":false},{"id":271015,"name":"Gerald T. Nepom","orcid":"0000-0002-8063-1464","position":4,"is_corresponding":false},{"id":692109,"name":"Vivian H. Gersuk","orcid":"0000-0003-4123-9926","position":5,"is_corresponding":false},{"id":1264640,"name":"B A Fuchs","orcid":"0000-0002-2910-2735","position":6,"is_corresponding":false},{"id":308289,"name":"S. Alice Long","orcid":"0000-0002-0281-1240","position":7,"is_corresponding":false},{"id":308290,"name":"Peter S. Linsley","orcid":"0000-0002-8960-4307","position":8,"is_corresponding":false},{"id":1264639,"name":"Erin M. Witkop","orcid":"0000-0002-4117-7334","position":0,"is_corresponding":true}],"reference_count":68,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:01:59.101070Z","pmid":"38937521","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":[]}