CD8+ T cells cause disability and axon loss in a mouse model of multiple sclerosis
| Autor: | Moses Rodriguez, Chandra Deb, Christopher L. German, Reghann G. LaFrance-Corey, Anthony J. Windebank, Charles L. Howe, William F. Schmalstieg, Brian M. Sauer, Huan Wang |
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| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Male
Pathology medicine.medical_specialty Adoptive cell transfer Multiple Sclerosis T cell Central nervous system lcsh:Medicine Neurological Disorders/Multiple Sclerosis and Related Disorders CD8-Positive T-Lymphocytes Motor Activity Biology Mice Histocompatibility Antigens Leukocytes medicine Animals Cytotoxic T cell Axon lcsh:Science Multidisciplinary Perforin Multiple sclerosis lcsh:R Motor Cortex Spinal cord medicine.disease Axons Disease Models Animal medicine.anatomical_structure Gene Expression Regulation Spinal Cord Immunology/Immune Response Female lcsh:Q Neuroscience/Neurobiology of Disease and Regeneration Neuroscience CD8 Demyelinating Diseases Research Article |
| Zdroj: | PLoS ONE, Vol 5, Iss 8, p e12478 (2010) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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