{"doi":"10.1101/2025.08.05.25333071","title":"Intrathecally expanded GZMK+/GZMH+ CD8 T cells targeting EBV antigens may reduce severity of Multiple Sclerosis","abstract":"Combining cerebrospinal fluid B cell receptor and T cell receptor repertoire analysis with transcriptional/ flow cytometry cellular profiles in hundreds of deeply-phenotyped people with Multiple Sclerosis (pwMS) and controls, we identified intrathecal expansion of anti-viral, cytotoxic, granzymes H/K (GZMH+/GZMK+) double positive (DP) CD8+ T cells that recognize EBV epitopes in pwMS. DP CD8+ T cells are activated and expanded by, and kill autologous, EBV-infected CSF B cell lines in-vitro. Correlations of surrogate transcriptional profiles with clinical and imaging outcomes infer a beneficial role for EBV-targeting DP CD8+ T cells, as untreated pwMS with proportionally higher DP CD8+ T cells to intrathecal B cells accumulate neurological disability slower. MS therapies also increase ratios of beneficial CD8+ T cell responses to intrathecal B cells, consistent with their ability to inhibit disability progression. This study provides indirect evidence that intrathecal EBV infection participates in disability accumulation in pwMS.","journal":"medRxiv","year":2025,"id":556659,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9578,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":347272,"name":"Péter Kósa","orcid":"0000-0002-1392-0629","position":1,"is_corresponding":false},{"id":266859,"name":"Francisco Otaizo‐Carrasquero","orcid":"0000-0001-7518-173X","position":2,"is_corresponding":false},{"id":261528,"name":"Dan E. Sturdevant","orcid":null,"position":3,"is_corresponding":false},{"id":813204,"name":"Amirhossein Shamsaddini","orcid":"0000-0002-7830-304X","position":4,"is_corresponding":false},{"id":228426,"name":"Yongmei Zhao","orcid":"0000-0003-0800-4658","position":5,"is_corresponding":false},{"id":1456348,"name":"Jyothi Shetty","orcid":"0000-0002-4523-7437","position":6,"is_corresponding":false},{"id":108657,"name":"Craig Martens","orcid":"0000-0001-8112-2234","position":7,"is_corresponding":false},{"id":104194,"name":"Jeffrey I. Cohen","orcid":"0000-0003-0238-7176","position":8,"is_corresponding":false},{"id":347281,"name":"Bibiana Bielekova","orcid":"0000-0002-0959-9430","position":9,"is_corresponding":false},{"id":1326826,"name":"Shinji Ashida","orcid":"0000-0002-2287-2649","position":0,"is_corresponding":true}],"reference_count":64,"raw_metadata":null,"created_at":"2026-07-19T02:55:13.130091Z","pmid":"40970118","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":[]}