TY  - JOUR
A1  - Ip, Chi Wang
A1  - Kroner, Antje
A1  - Groh, Janos
A1  - Huber, Marianne
A1  - Klein, Dennis
A1  - Spahn, Irene
A1  - Diem, Ricarda
A1  - Williams, Sarah K.
A1  - Nave, Klaus-Armin
A1  - Edgar, Julia M.
A1  - Martini, Rudolf
T1  - Neuroinflammation by Cytotoxic T-Lymphocytes Impairs Retrograde Axonal Transport in an Oligodendrocyte Mutant Mouse
JF  - PLoS One
N2  - 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 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.
KW  - myelin
KW  - experimental autoimmune encephalomyelitis
KW  - degeneration
KW  - axonopathic changes
KW  - neural apoptosis
KW  - nervous system
KW  - motor function
KW  - proteolipid protein gene
KW  - retinal ganglion cells
KW  - granzyme B
KW  - multiple sclerosis
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-134982
VL  - 7
IS  - 8
ER  -