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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 CD8\u03b1 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.<\/jats:p>","DOI":"10.1084\/jem.20221862","type":"journal-article","created":{"date-parts":[[2023,5,27]],"date-time":"2023-05-27T02:20:57Z","timestamp":1685154057000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":7,"title":["CD8+ T cell depletion prevents neuropathology in a mouse model of globoid cell leukodystrophy"],"prefix":"10.1084","volume":"220","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0186-6087","authenticated-orcid":true,"given":"Pearl A.","family":"Sutter","sequence":"first","affiliation":[{"name":"University of Connecticut School of Medicine 1 Department of Neuroscience, , Farmington, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1559-7159","authenticated-orcid":true,"given":"Antoine","family":"M\u00e9noret","sequence":"additional","affiliation":[{"name":"University of Connecticut School of Medicine 2 Department of Immunology, , Farmington, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2674-1605","authenticated-orcid":true,"given":"Evan R.","family":"Jellison","sequence":"additional","affiliation":[{"name":"University of Connecticut School of Medicine 2 Department of Immunology, , Farmington, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7160-5988","authenticated-orcid":true,"given":"Alexandra M.","family":"Nicaise","sequence":"additional","affiliation":[{"name":"University of Connecticut School of Medicine 1 Department of Neuroscience, , Farmington, CT, USA"},{"id":[{"id":"https:\/\/ror.org\/013meh722","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Cambridge 3 Department of Clinical Neuroscience and National Institute for Health Research Biomedical Research Centre, , Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8268-3743","authenticated-orcid":true,"given":"Allison M.","family":"Bradbury","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/003rfsp33","id-type":"ROR","asserted-by":"publisher"}],"name":"Nationwide Children's Hospital, Ohio State University 4 Department of Pediatrics, , Columbus, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4600-5504","authenticated-orcid":true,"given":"Anthony T.","family":"Vella","sequence":"additional","affiliation":[{"name":"University of Connecticut School of Medicine 2 Department of Immunology, , Farmington, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1664-6634","authenticated-orcid":true,"given":"Ernesto R.","family":"Bongarzone","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02mpq6x41","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Illinois at Chicago 5 Department of Anatomy and Cell Biology, , Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4529-1385","authenticated-orcid":true,"given":"Stephen J.","family":"Crocker","sequence":"additional","affiliation":[{"name":"University of Connecticut School of Medicine 1 Department of Neuroscience, , Farmington, CT, USA"},{"name":"University of Connecticut School of Medicine 2 Department of Immunology, , Farmington, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2023,6,13]]},"reference":[{"key":"2023061313350455200_bib1","doi-asserted-by":"publisher","first-page":"1272","DOI":"10.4049\/jimmunol.2100737","article-title":"Transcriptomic profiling identifies CD8+ T cells in the brain of aged and alzheimer\u2019s disease transgenic mice as tissue-resident memory T cells","volume":"209","author":"Altendorfer","year":"2022","journal-title":"J. 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