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CD8+ T cell depletion prevents neuropathology in a mouse model of globoid cell leukodystrophy.

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.

SUBMITTER: Sutter PA

PROVIDER: S-EPMC10266545 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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CD8+ T cell depletion prevents neuropathology in a mouse model of globoid cell leukodystrophy.

Sutter Pearl A PA Ménoret Antoine A Jellison Evan R ER Nicaise Alexandra M AM Bradbury Allison M AM Vella Anthony T AT Bongarzone Ernesto R ER Crocker Stephen J SJ

The Journal of experimental medicine 20230613 9

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 ...[more]

PMID: 37310382

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