CD8+ T cell depletion prevents neuropathology in a mouse model of globoid cell leukodystrophy
© 2023 Sutter et al..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:220 |
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| Enthalten in: |
The Journal of experimental medicine - 220(2023), 9 vom: 04. Sept. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Sutter, Pearl A [VerfasserIn] |
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| Links: |
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| Themen: |
Antibodies, Blocking |
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| Anmerkungen: |
Date Completed 15.06.2023 Date Revised 22.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1084/jem.20221862 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM358120691 |
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| 520 | |a 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 | ||
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| 700 | 1 | |a Ménoret, Antoine |e verfasserin |4 aut | |
| 700 | 1 | |a Jellison, Evan R |e verfasserin |4 aut | |
| 700 | 1 | |a Nicaise, Alexandra M |e verfasserin |4 aut | |
| 700 | 1 | |a Bradbury, Allison M |e verfasserin |4 aut | |
| 700 | 1 | |a Vella, Anthony T |e verfasserin |4 aut | |
| 700 | 1 | |a Bongarzone, Ernesto R |e verfasserin |4 aut | |
| 700 | 1 | |a Crocker, Stephen J |e verfasserin |4 aut | |
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