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

Autor:	Sutter PA; Department of Neuroscience, University of Connecticut School of Medicine, Farmington, CT, USA., Ménoret A; Department of Immunology, University of Connecticut School of Medicine, Farmington, CT, USA., Jellison ER; Department of Immunology, University of Connecticut School of Medicine, Farmington, CT, USA., Nicaise AM; Department of Neuroscience, University of Connecticut School of Medicine, Farmington, CT, USA.; Department of Clinical Neuroscience and National Institute for Health Research Biomedical Research Centre, University of Cambridge, Cambridge, UK., Bradbury AM; Department of Pediatrics, Nationwide Children's Hospital, Ohio State University, Columbus, OH, USA., Vella AT; Department of Immunology, University of Connecticut School of Medicine, Farmington, CT, USA., Bongarzone ER; Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, IL, USA., Crocker SJ; Department of Neuroscience, University of Connecticut School of Medicine, Farmington, CT, USA.; Department of Immunology, University of Connecticut School of Medicine, Farmington, CT, USA.
Jazyk:	angličtina
Zdroj:	The Journal of experimental medicine [J Exp Med] 2023 Sep 04; Vol. 220 (9). Date of Electronic Publication: 2023 Jun 13.
DOI:	10.1084/jem.20221862
Abstrakt:	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. (© 2023 Sutter et al.)
Databáze:	MEDLINE
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