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Neuroinflammation by Cytotoxic T-Lymphocytes Impairs Retrograde Axonal Transport in an Oligodendrocyte Mutant Mouse

Please always quote using this URN: urn:nbn:de:bvb:20-opus-134982
  • Mice overexpressing proteolipid protein (PLP) develop a leukodystrophy-like disease involving cytotoxic, CD8+ T-lymphocytes. Here we show that these cytotoxic T-lymphocytes perturb retrograde axonal transport. Using fluorogold stereotactically injected into the colliculus superior, we found that PLP overexpression in oligodendrocytes led to significantly reduced retrograde axonal transport in retina ganglion cell axons. We also observed an accumulation of mitochondria in the juxtaparanodal axonal swellings, indicative for a disturbed axonalMice overexpressing proteolipid protein (PLP) develop a leukodystrophy-like disease involving cytotoxic, CD8+ T-lymphocytes. Here we show that these cytotoxic T-lymphocytes perturb retrograde axonal transport. Using fluorogold stereotactically injected into the colliculus superior, we found that PLP overexpression in oligodendrocytes led to significantly reduced retrograde axonal transport in retina ganglion cell axons. We also observed an accumulation of mitochondria in the juxtaparanodal axonal swellings, indicative for a disturbed axonal transport. PLP overexpression in the absence of T-lymphocytes rescued retrograde axonal transport defects and abolished axonal swellings. Bone marrow transfer from wildtype mice, but not from perforin- or granzyme B-deficient mutants, into lymphocyte-deficient PLP mutant mice led again to impaired axonal transport and the formation of axonal swellings, which are predominantly located at the juxtaparanodal region. This demonstrates that the adaptive immune system, including cytotoxic T-lymphocytes which release perforin and granzyme B, are necessary to perturb axonal integrity in the PLP-transgenic disease model. Based on our observations, so far not attended molecular and cellular players belonging to the immune system should be considered to understand pathogenesis in inherited myelin disorders with progressive axonal damage.show moreshow less

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Metadaten
Author: Chi Wang Ip, Antje Kroner, Janos Groh, Marianne Huber, Dennis Klein, Irene Spahn, Ricarda Diem, Sarah K. Williams, Klaus-Armin Nave, Julia M. Edgar, Rudolf Martini
URN:urn:nbn:de:bvb:20-opus-134982
Document Type:Journal article
Faculties:Medizinische Fakultät / Neurologische Klinik und Poliklinik
Language:English
Parent Title (English):PLoS One
Year of Completion:2012
Volume:7
Issue:8
Pagenumber:e42554
Source:PLoS ONE 7(8): e42554. doi:10.1371/journal.pone.0042554
DOI:https://doi.org/10.1371/journal.pone.0042554
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 616 Krankheiten
Tag:axonopathic changes; degeneration; experimental autoimmune encephalomyelitis; granzyme B; motor function; multiple sclerosis; myelin; nervous system; neural apoptosis; proteolipid protein gene; retinal ganglion cells
Release Date:2017/12/17
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung