{"doi":"10.7554/elife.76339","title":"A CD4+ T cell reference map delineates subtype-specific adaptation during acute and chronic viral infections","abstract":"CD4 + T cells are critical orchestrators of immune responses against a large variety of pathogens, including viruses. While multiple CD4 + T cell subtypes and their key transcriptional regulators have been identified, there is a lack of consistent definition for CD4 + T cell transcriptional states. In addition, the progressive changes affecting CD4 + T cell subtypes during and after immune responses remain poorly defined. Using single-cell transcriptomics, we characterized the diversity of CD4 + T cells responding to self-resolving and chronic viral infections in mice. We built a comprehensive map of virus-specific CD4 + T cells and their evolution over time, and identified six major cell states consistently observed in acute and chronic infections. During the course of acute infections, T cell composition progressively changed from effector to memory states, with subtype-specific gene modules and kinetics. Conversely, in persistent infections T cells acquired distinct, chronicity-associated programs. By single-cell T cell receptor (TCR) analysis, we characterized the clonal structure of virus-specific CD4 + T cells across individuals. Virus-specific CD4 + T cell responses were essentially private across individuals and most T cells differentiated into both Tfh and Th1 subtypes irrespective of their TCR. Finally, we showed that our CD4 + T cell map can be used as a reference to accurately interpret cell states in external single-cell datasets across tissues and disease models. Overall, this study describes a previously unappreciated level of adaptation of the transcriptional states of CD4 + T cells responding to viruses and provides a new computational resource for CD4 + T cell analysis.","journal":"eLife","year":2022,"id":238344,"datarank":1.674213337170028,"base_score":4.02535169073515,"endowment":4.02535169073515,"self_citation_contribution":0.6038027536102726,"citation_network_contribution":1.0704105835597555,"self_endowment_contribution":0.6038027536102726,"citer_contribution":1.0704105835597555,"corpus_percentile":null,"corpus_rank":null,"citation_count":55,"citer_count":52,"citers_with_citation_signal":43,"citers_with_endowment":43,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9471,"is_data_producer":true,"deposit_databanks":{"GEO":["GSE182320","GSE200635","GSE158896","GSE134157","GSE121002"],"figshare":["10.6084/m9.figshare.16592693"]},"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":830133,"name":"Ariel Tjitropranoto","orcid":"0000-0001-5525-5236","position":1,"is_corresponding":false},{"id":431383,"name":"Zachary Sherman","orcid":null,"position":2,"is_corresponding":false},{"id":226280,"name":"Michael C. Kelly","orcid":"0000-0003-0654-2778","position":3,"is_corresponding":false},{"id":299367,"name":"Thomas Ciucci","orcid":"0000-0002-5828-0207","position":4,"is_corresponding":false},{"id":623745,"name":"Santiago J. Carmona","orcid":"0000-0002-2495-0671","position":5,"is_corresponding":false},{"id":274864,"name":"Massimo Andreatta","orcid":"0000-0002-8036-2647","position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":null,"created_at":"2026-07-19T00:22:26.932537Z","pmid":"35829695","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":[]}