CD8+ T cells cause disability and axon loss in a mouse model of multiple sclerosis

Chandra Deb, Reghann G. Lafrance-Corey, William F. Schmalstieg, Brian M. Sauer, Huan Wang, Christopher L. German, Anthony J. Windebank, Moses Rodriguez, Charles L. Howe

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Background: The objective of this study was to test the hypothesis that CD8+ T cells directly mediate motor disability and axon injury in the demyelinated central nervous system. We have previously observed that genetic deletion of the CD8+ T cell effector molecule perforin leads to preservation of motor function and preservation of spinal axons in chronically demyelinated mice. Methodology/Principal Findings: To determine if CD8+ T cells are necessary and sufficient to directly injure demyelinated axons, we adoptively transferred purified perforin-competent CD8+ spinal cord-infiltrating T cells into profoundly demyelinated but functionally preserved perforin-deficient host mice. Transfer of CD8+ spinal cord-infiltrating T cells rapidly and irreversibly impaired motor function, disrupted spinal cord motor conduction, and reduced the number of mediumand large-caliber spinal axons. Likewise, immunodepletion of CD8+ T cells from chronically demyelinated wildtype mice preserved motor function and limited axon loss without altering other disease parameters. Conclusions/Significance: In multiple sclerosis patients, CD8+ T cells outnumber CD4+ T cells in active lesions and the number of CD8+ T cells correlates with the extent of ongoing axon injury and functional disability. Our findings suggest that CD8+ T cells may directly injure demyelinated axons and are therefore a viable therapeutic target to protect axons and motor function in patients with multiple sclerosis.

Original languageEnglish (US)
Article numbere12478
JournalPloS one
Volume5
Issue number8
DOIs
StatePublished - 2010

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Deb, C., Lafrance-Corey, R. G., Schmalstieg, W. F., Sauer, B. M., Wang, H., German, C. L., Windebank, A. J., Rodriguez, M., & Howe, C. L. (2010). CD8+ T cells cause disability and axon loss in a mouse model of multiple sclerosis. PloS one, 5(8), [e12478]. https://doi.org/10.1371/journal.pone.0012478