CNS-irrelevant T-cells enter the brain, cause blood-brain barrier disruption but no glial pathology.
Invasion of autoreactive T-cells and alterations of the blood-brain barrier (BBB) represent early pathological manifestations of multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE). Non-CNS-specific T-cells are also capable of entering the CNS. However, studies investigating the spatial pattern of BBB alterations as well as the exact localization and neuropathological consequences of transferred non-CNS-specific cells have been thus far lacking. Here, we used magnetic resonance imaging and multiphoton microscopy, as well as histochemical and high-precision unbiased stereological analyses to compare T-cell transmigration, localization, persistence, relation to BBB disruption and subsequent effects on CNS tissue in a model of T-cell transfer of ovalbumin (OVA)- and proteolipid protein (PLP)-specific T-cells. BBB alterations were present in both EAE-mice and mice transferred with OVA-specific T-cells. In the latter case, BBB alterations were less pronounced, but the pattern of initial cell migration into the CNS was similar for both PLP- and OVA-specific cells [mean (SEM), 95 x 10(3) (7.6 x 10(3)) and 88 x 10(3) (18 x 10(3)), respectively]. Increased microglial cell density, astrogliosis and demyelination were, however, observed exclusively in the brain of EAE-mice. While mice transferred with non-neural-specific cells showed similar levels of rhodamine-dextran extravasation in susceptible brain regions, EAE-mice presented huge BBB disruption in brainstem and moderate leakage in cerebellum. This suggests that antigen specificity and not the absolute number of infiltrating cells determine the magnitude of BBB disruption and glial pathology.
Smorodchenko
Alina
A
Cecilie-Vogt-Clinic for Molecular Neurology, Charité-Universitaetsmedizin Berlin and Max-Delbrueck-Center for Molecular Medicine, Berlin, Germany.
Wuerfel
Jens
J
Pohl
Elena E
EE
Vogt
Johannes
J
Tysiak
Eva
E
Glumm
Robert
R
Hendrix
Sven
S
Nitsch
Robert
R
Zipp
Frauke
F
Infante-Duarte
Carmen
C
D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology*; D001921:Brain / Q000166:cytology* / Q000502:physiology*; D002452:Cell Count; D002490:Central Nervous System / Q000166:cytology / Q000502:physiology; D003627:Data Interpretation, Statistical; D004660:Encephalitis / Q000473:pathology; D005260:Female; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D051379:Mice; D008810:Mice, Inbred C57BL; D036641:Microscopy, Fluorescence, Multiphoton; D018991:Myelin Proteolipid Protein / Q000276:immunology; D009457:Neuroglia / Q000502:physiology*; D010047:Ovalbumin / Q000276:immunology; D010539:Permeability; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*
D018991:Myelin Proteolipid Protein; D010047:Ovalbumin