{"doi":"10.1101/2022.09.30.510367","title":"Therapeutic depletion of CD8+ T-cells prevents myelin pathology in Globoid Cell Leukodystrophy","abstract":"Abstract Globoid cell leukodystrophy (GLD) or Krabbe’s disease is a fatal genetic demyelinating disease of the central nervous system caused by loss-of-function mutations in the galactosylceramidase (galc) gene. While the metabolic basis for disease is known, the understanding of how this results in neuropathology is not well understood. Herein we report that the rapid and protracted elevation of CD8+ cytotoxic T lymphocytes occurs coincident with clinical disease in a mouse model of GLD. Administration of a function blocking antibody against CD8α effectively prevented disease onset, reduced morbidity and mortality and prevented CNS demyelination in mice. These data indicate that subsequent to the genetic cause of disease, neuropathology is driven by pathogenic CD8+ T cells, thus offering novel therapeutic potential for treatment of GLD. One-Sentence Summary CD8 T-cells mediate demyelination and neuroinflammation in a genetic white matter disease.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":312086,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9557,"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":516377,"name":"Antoine Ménoret","orcid":"0000-0002-1559-7159","position":1,"is_corresponding":false},{"id":305930,"name":"Evan R. Jellison","orcid":"0009-0004-2674-1605","position":2,"is_corresponding":false},{"id":305927,"name":"Alexandra M. Nicaise","orcid":"0000-0001-7160-5988","position":3,"is_corresponding":false},{"id":308927,"name":"Allison M. Bradbury","orcid":"0000-0002-8268-3743","position":4,"is_corresponding":false},{"id":250005,"name":"Anthony T. Vella","orcid":"0000-0003-4600-5504","position":5,"is_corresponding":false},{"id":305928,"name":"Ernesto R. Bongarzone","orcid":"0000-0003-1664-6634","position":6,"is_corresponding":false},{"id":305934,"name":"Stephen J. Crocker","orcid":"0000-0003-4529-1385","position":7,"is_corresponding":false},{"id":305931,"name":"Pearl A. Sutter","orcid":"0000-0003-0186-6087","position":0,"is_corresponding":true}],"reference_count":33,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:33:32.327694Z","pmid":null,"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":[]}