First Author | Deb C | Year | 2010 |
Journal | PLoS One | Volume | 5 |
Issue | 8 | Pages | e12478 |
PubMed ID | 20814579 | Mgi Jnum | J:163992 |
Mgi Id | MGI:4830385 | Doi | 10.1371/journal.pone.0012478 |
Citation | Deb C, et al. (2010) CD8+ T cells cause disability and axon loss in a mouse model of multiple sclerosis. PLoS One 5(8) |
abstractText | 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 medium- and 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. |