Abstract
Although multiple sclerosis is a common neurological disorder, the origin of the autoimmune response against myelin, which is the characteristic feature of the disease, remains unclear. To investigate whether oligodendrocyte death could cause this autoimmune response, we examined the oligodendrocyte ablation Plp1-CreER T;ROSA26-eGFP-DTA (DTA) mouse model. Approximately 30 weeks after recovering from oligodendrocyte loss and demyelination, DTA mice develop a fatal secondary disease characterized by extensive myelin and axonal loss. Strikingly, late-onset disease was associated with increased numbers of T lymphocytes in the CNS and myelin oligodendrocyte glycoprotein (MOG)-specific T cells in lymphoid organs. Transfer of T cells derived from DTA mice to naive recipients resulted in neurological defects that correlated with CNS white matter inflammation. Furthermore, immune tolerization against MOG ameliorated symptoms. Overall, these data indicate that oligodendrocyte death is sufficient to trigger an adaptive autoimmune response against myelin, suggesting that a similar process can occur in the pathogenesis of multiple sclerosis.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 65-74 |
| Number of pages | 10 |
| Journal | Nature neuroscience |
| Volume | 19 |
| Issue number | 1 |
| DOIs | |
| State | Published - Dec 29 2015 |
Funding
We thank E. Liu, A. Solanki, A.X. Tang and S. Labak for technical assistance, G. Wright for assistance with the morphometric analysis of the EM images using the ImageJ software and V. Bindokas from the University of Chicago Integrated Light Microscopy Core Facility for help with image acquisition and image processing. The work was supported by awards from the Myelin Repair Foundation and the National Multiple Sclerosis Society (RG 4952-A-5) to B.P. and S.D.M.
ASJC Scopus subject areas
- General Neuroscience