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

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 CD8 alpha 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. Globoid cell leukodystrophy (GLD) is an incurable genetic disease characterized by profound white matter loss and inflammation. This report identifies CD8(+) T cells as a novel pathogenic process in the clinical development and neuropathology of this disease.

Automated summary

Globoid cell leukodystrophy (GLD), or Krabbe's disease, is a fatal genetic demyelinating disease caused by loss-of-function mutations in the galactosylceramidase (galc) gene. A study conducted on a mouse model of GLD has identified CD8(+) cytotoxic T lymphocytes as a key player in the development of the disease and its neuropathology. Blocking CD8 alpha effectively prevented disease onset, reduced morbidity and mortality, and prevented CNS demyelination in mice, suggesting potential novel therapeutic targets for GLD.