{"doi":"10.1016/j.celrep.2022.111736","title":"Spatial transcriptomics demonstrates the role of CD4 T cells in effector CD8 T cell differentiation during chronic viral infection","abstract":"CD4 T cell help is critical to sustain effector CD8 T cell responses during chronic infection, notably via T follicular helper (Tfh)-derived interleukin-21 (IL-21). Conversely, CD4 depletion results in severe CD8 T cell dysfunction and lifelong viremia despite CD4 T cell reemergence following transient depletion. These observations suggest that repopulating CD4 subsets are functionally or numerically insufficient to orchestrate a robust CD8 response. We utilize spatial transcriptomics and single-cell RNA sequencing (scRNA-seq) to investigate CD4 T cell heterogeneity under CD4-replete and -deplete conditions and explore cellular interactions during chronic infection. Although IL-21-producing Tfh cells repopulate following transient CD4 depletion, they are outnumbered by immunomodulatory CD4 T cells. Moreover, the splenic architecture appears perturbed, with decreases in white pulp regions, coinciding with germinal center losses. These disruptions in splenic architecture are associated with diminished Tfh and progenitor CD8 T cell colocalization, providing a potential mechanism for impaired progenitor-to-effector CD8 T cell differentiation during \"un-helped\" conditions.","journal":"Cell Reports","year":2022,"id":253924,"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":22,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9485,"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":302501,"name":"Moujtaba Y. Kasmani","orcid":"0000-0002-5753-5335","position":2,"is_corresponding":false},{"id":810161,"name":"Christine Nguyen","orcid":"0000-0002-5750-8134","position":3,"is_corresponding":false},{"id":900019,"name":"Ashley K. Brown","orcid":"0000-0002-1320-9327","position":4,"is_corresponding":false},{"id":900020,"name":"Siying Lin","orcid":"0000-0002-9993-7957","position":5,"is_corresponding":false},{"id":270587,"name":"Robert Burns","orcid":"0000-0001-5334-3486","position":6,"is_corresponding":false},{"id":302507,"name":"Weiguo Cui","orcid":"0000-0003-1562-9218","position":7,"is_corresponding":false},{"id":349890,"name":"Paytsar Topchyan","orcid":"0000-0002-3902-7652","position":0,"is_corresponding":true}],"reference_count":67,"raw_metadata":null,"created_at":"2026-07-19T00:24:59.596040Z","pmid":"36450262","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":[]}