Immune cells contribute to myelin degeneration and axonopathic changes in mice overexpressing proteolipid protein in oligodendrocytes

Research output: Journal contributionsJournal articlesResearchpeer-review

Authors

  • Chi Wang Ip
  • Antje Kroner
  • Martin Bendszus
  • Christoph Leder
  • Igor Kobsar
  • Stefan Fischer
  • Heinz Wiendl
  • Klaus-Armin Nave
  • Rudolf Martini
Overexpression of the major myelin protein of the CNS, proteolipid protein (PLP), leads to late-onset degeneration of myelin and pathological changes in axons. Based on the observation that in white matter tracts of these mutants both CD8+ T-lymphocytes and CD11b+ macrophage-like cells are numerically elevated, we tested the hypothesis that these cells are pathologically involved in the primarily genetically caused neuropathy. Using flow cytometry of mutant brains, CD8+ cells could be identified as activated effector cells, and confocal microscopy revealed a close association of the T-cells with MHC-I+ (major histocompatibility complex class I positive) oligodendrocytes. Crossbreeding the myelin mutants with mice deficient in the recombination activating gene-1 (RAG-1) lacking mature T- and B-lymphocytes led to a reduction of the number of CD11b+ cells and to a substantial alleviation of pathological changes. In accordance with these findings, magnetic resonance imaging revealed less ventricular enlargement in the double mutants, partially because of more preserved corpora callosa. To investigate the role of CD8+ versus CD4+ T-lymphocytes, we reconstituted the myelin-RAG-1 double mutants with bone marrow from either CD8-negative (CD4+) or CD4-negative (CD8+) mice. The severe ventricular enlargement was only found when the double mutants were reconstituted with bone marrow from CD8+ mice, suggesting that the CD8+ lymphocytes play a critical role in the immune-related component of myelin degeneration in the mutants. These findings provide strong evidence that a primary glial damage can cause secondary immune reactions of pathological significance as it has been suggested for some forms of multiple sclerosis and other leukodystrophies.
Original languageEnglish
JournalThe Journal of Neuroscience
Volume26
Issue number31
Pages (from-to)8206-8216
Number of pages11
ISSN0270-6474
DOIs
Publication statusPublished - 02.08.2006
Externally publishedYes

Bibliographical note

https://www.jneurosci.org/content/rights-permissions

    Research areas

  • Biology - microglia, macrophages, T-lymphocytes, leukodystrophy, multiple sclerosis, animal model, inflammation

Recently viewed

Publications

  1. “Have you felt angry lately?”
  2. Helsingør statement on poly- and perfluorinated alkyl substances (PFASs)
  3. Continuous pretreatment, hydrolysis, and fermentation of organic residues for the production of biochemicals
  4. Actor-Network Theory II
  5. Home range and habitat use by the pacas (Cuniculus paca) in a montane tropical forest in Bolivia
  6. Do unbiased people act more rationally? - The case of comparative realism and vaccine intention
  7. Selbstbild und Selbstvertrauen
  8. Influence of spectrally selective solar cells on microalgae growth in photo-bioreactors
  9. Do high incomes reflect individual performance?
  10. Make it your Break! Benefits of Person-Break Fit for Post-Break Affect
  11. Kunst und Klasse
  12. Ground Truthing in Digital Technoculture
  13. SEIS
  14. Postretirement Career Planning
  15. Complexity in Water Management and Governance
  16. How small business managers’ age and focus on opportunities affect business growth
  17. Predicting individual plant performance in grasslands
  18. Sustainable software products—Towards assessment criteria for resource and energy efficiency
  19. Soziale und kulturelle Differenz
  20. Abiotic and biotic degradation of five aromatic organosilicon compounds in aqueous media
  21. Trade Dynamics and Trade Costs
  22. Erving Goffman: Social Embarrassment and Social Organization
  23. Employees’ perceived benefits from participating in CSR activities and implications for increasing employees engagement in CSR
  24. 'You're-like-wind-blowing-over-the-land-and-passing-on'
  25. Hybrid joining of cast aluminum and sheet steel using refill friction stir spot welding with strength enhancement via adhesive application
  26. Zwischen Selbstvermarktung und Subversion. Das Web 2.0 und seine Subjekte
  27. An assessment of The Natural Step theory of sustainability
  28. Exports, R&D and productivity
  29. Pre-startup planning sophistication and its impact an new venture performance in Germany
  30. Kunstvermittlung im System Kunst
  31. Historical ecology meets conservation and evolutionary genetics
  32. Neuartige Spurenstoffe im Wasser
  33. Frontier settlement and cultural change
  34. Action regulation theory: Foundations, current knowledge, and future directions
  35. Resonance and reach
  36. Debating accounting and sustainability: from incompatibility to rapprochement in the pursuit of corporate sustainability
  37. Verloren im Cyberspace
  38. Bildung für nachhaltige Entwicklung zum Thema „Wasser“
  39. Genetic erosion in habitat specialist shows need to protect large peat bogs
  40. Efficiency of rational learning with private information