{"doi":"10.4049/jimmunol.2001348","title":"Identification of a T-bethi Quiescent Exhausted CD8 T Cell Subpopulation That Can Differentiate into TIM3+CX3CR1+ Effectors and Memory-like Cells","abstract":"Abstract Persistent Ag induces a dysfunctional CD8 T cell state known as “exhaustion” characterized by PD-1 expression. Nevertheless, exhausted CD8 T cells retain functionality through continued differentiation of progenitor into effector cells. However, it remains ill-defined how CD8 T cell effector responses are sustained in situ. In this study, we show using the mouse chronic lymphocytic choriomeningitis virus infection model that CX3CR1+ CD8 T cells contain a T-bet–dependent TIM3−PD-1lo subpopulation that is distinct from the TIM3+CX3CR1+PD-1+ proliferative effector subset. The TIM3−CX3CR1+ cells are quiescent and express a low but significant level of the transcription factor TCF-1, demonstrating similarity to TCF-1hi progenitor CD8 T cells. Furthermore, following the resolution of lymphocytic choriomeningitis virus viremia, a substantial proportion of TCF-1+ memory-like CD8 T cells show evidence of CX3CR1 expression during the chronic phase of the infection. Our results suggest a subset of the CX3CR1+ exhausted population demonstrates progenitor-like features that support the generation of the CX3CR1+ effector pool from the TCF-1hi progenitors and contribute to the memory-like pool following the resolution of viremia.","journal":"The Journal of Immunology","year":2021,"id":167922,"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":31,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9567,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":564288,"name":"Yu Xia","orcid":"0000-0002-6397-1205","position":1,"is_corresponding":false},{"id":237496,"name":"Bence Dániel","orcid":"0000-0002-2410-8767","position":2,"is_corresponding":false},{"id":227860,"name":"Kathryn E. Yost","orcid":"0000-0001-6807-950X","position":3,"is_corresponding":false},{"id":564289,"name":"Elliot Bradshaw","orcid":"0000-0002-5477-5309","position":4,"is_corresponding":false},{"id":564290,"name":"Elena Tonc","orcid":"0000-0002-6604-6496","position":5,"is_corresponding":false},{"id":564291,"name":"Daniel Verbaro","orcid":"0000-0001-5624-2488","position":6,"is_corresponding":false},{"id":623479,"name":"Kohei Kometani","orcid":"0000-0003-4281-4371","position":7,"is_corresponding":false},{"id":276885,"name":"Wayne M. Yokoyama","orcid":"0000-0002-0566-7264","position":8,"is_corresponding":false},{"id":623480,"name":"Tomohiro Kurosaki","orcid":"0000-0002-6352-304X","position":9,"is_corresponding":false},{"id":21653,"name":"Ansuman T. Satpathy","orcid":"0000-0002-5167-537X","position":10,"is_corresponding":false},{"id":564292,"name":"Takeshi Egawa","orcid":"0000-0001-7489-1051","position":11,"is_corresponding":false},{"id":564287,"name":"Saravanan Raju","orcid":"0000-0003-3216-5574","position":0,"is_corresponding":true}],"reference_count":53,"raw_metadata":null,"created_at":"2026-07-18T23:46:02.603031Z","pmid":"34088768","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":[]}