title: CD8+ T cells cause disability and axon loss in a mouse model of multiple sclerosis.
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.
  
  
  RESULTS
  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
  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.
authors.affiliation: Department of Neurology, Mayo Clinic College of Medicine, Rochester, Minnesota, United States of America.
authors.forename: Chandra
authors.initials: C
authors.lastname: Deb
authors.forename: Reghann G
authors.initials: RG
authors.lastname: Lafrance-Corey
authors.forename: William F
authors.initials: WF
authors.lastname: Schmalstieg
authors.forename: Brian M
authors.initials: BM
authors.lastname: Sauer
authors.forename: Huan
authors.initials: H
authors.lastname: Wang
authors.forename: Christopher L
authors.initials: CL
authors.lastname: German
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Windebank
authors.forename: Moses
authors.initials: M
authors.lastname: Rodriguez
authors.forename: Charles L
authors.initials: CL
authors.lastname: Howe
mesh_terms: D000818:Animals; D001369:Axons / Q000276:immunology* / Q000473:pathology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D003711:Demyelinating Diseases / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D006649:Histocompatibility Antigens / Q000378:metabolism; D007962:Leukocytes / Q000276:immunology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000276:immunology* / Q000502:physiology*; D009044:Motor Cortex / Q000473:pathology; D009103:Multiple Sclerosis / Q000276:immunology / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D054353:Perforin / Q000172:deficiency / Q000378:metabolism; D013116:Spinal Cord / Q000473:pathology
chemical_list: D006649:Histocompatibility Antigens; D054353:Perforin
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