{"doi":"10.1084/jem.20220679","title":"Clonal lineage tracing reveals mechanisms skewing CD8+ T cell fate decisions in chronic infection","abstract":"Although recent evidence demonstrates heterogeneity among CD8+ T cells during chronic infection, developmental relationships and mechanisms underlying their fate decisions remain incompletely understood. Using single-cell RNA and TCR sequencing, we traced the clonal expansion and differentiation of CD8+ T cells during chronic LCMV infection. We identified immense clonal and phenotypic diversity, including a subset termed intermediate cells. Trajectory analyses and infection models showed intermediate cells arise from progenitor cells before bifurcating into terminal effector and exhausted subsets. Genetic ablation experiments identified that type I IFN drives exhaustion through an IRF7-dependent mechanism, possibly through an IFN-stimulated subset bridging progenitor and exhausted cells. Conversely, Zeb2 was critical for generating effector cells. Intriguingly, some T cell clones exhibited lineage bias. Mechanistically, we identified that TCR avidity correlates with an exhausted fate, whereas SHP-1 selectively restricts low-avidity effector cell accumulation. Thus, our work elucidates novel mechanisms underlying CD8+ T cell fate determination during persistent infection and suggests two potential pathways leading to exhaustion.","journal":"The Journal of Experimental Medicine","year":2022,"id":234916,"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":89,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.945,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":302502,"name":"Ryan Zander","orcid":"0000-0002-7431-8535","position":1,"is_corresponding":false},{"id":84628,"name":"H. Kay Chung","orcid":"0000-0002-7028-2432","position":2,"is_corresponding":false},{"id":851638,"name":"Yao Chen","orcid":"0000-0003-1409-5293","position":3,"is_corresponding":false},{"id":302500,"name":"Achia Khatun","orcid":"0000-0003-0525-4774","position":4,"is_corresponding":false},{"id":579397,"name":"Martina Damo","orcid":"0000-0002-7217-3221","position":5,"is_corresponding":false},{"id":349890,"name":"Paytsar Topchyan","orcid":"0000-0002-3902-7652","position":6,"is_corresponding":false},{"id":713276,"name":"K. E. Johnson","orcid":"0000-0002-8689-9170","position":7,"is_corresponding":false},{"id":851639,"name":"Darya Levashova","orcid":"0000-0001-5032-2006","position":8,"is_corresponding":false},{"id":270587,"name":"Robert Burns","orcid":"0000-0001-5334-3486","position":9,"is_corresponding":false},{"id":477165,"name":"Ulrike Lorenz","orcid":"0000-0002-7933-6855","position":10,"is_corresponding":false},{"id":658162,"name":"Vera L. Tarakanova","orcid":"0000-0002-9499-088X","position":11,"is_corresponding":false},{"id":499816,"name":"Nikhil S. Joshi","orcid":"0000-0002-7045-7837","position":12,"is_corresponding":false},{"id":267842,"name":"Susan M. Kaech","orcid":"0000-0002-3339-8698","position":13,"is_corresponding":false},{"id":302507,"name":"Weiguo Cui","orcid":"0000-0003-1562-9218","position":14,"is_corresponding":false},{"id":302501,"name":"Moujtaba Y. Kasmani","orcid":"0000-0002-5753-5335","position":0,"is_corresponding":true}],"reference_count":104,"raw_metadata":null,"created_at":"2026-07-19T00:21:42.662304Z","pmid":"36315049","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":[]}