Gimsa U. Peter SV. Lehmann K. Bechmann I. Nitsch R.
Axonal damage induced by invading T cells in organotypic central nervous system tissue in vitro: involvement of microglial cells, Brain Pathology. 10(3) :365-77, 2000.
Abstract
Neuroinflammation in the course of multiple sclerosis and experimental autoimmune encephalomyelitis results in demyelination and, recently demonstrated, axonal loss. Invading
neuroantigen specific T cells are the crucial cellular elements in these processes. Here we demonstrate that invasion of activated T cells induces a massive microglial attack on
myelinated axons in entorhinal-hippocampal slice cultures. Flow cytometry analysis of activation markers revealed that the activation state of invading MBP-specific T cells was
significantly lower in comparison to PMA-activated T cells. Moreover, MBP-specific T cells showed a significantly lower secretion of IFN-gamma. Conversely, MBP-specific T
cells displayed a significantly higher potential to trigger activation of microglial cells, i.e. upregulation of MHC class II and ICAM-1 expression, and, most importantly, microglial
phagocytosis of pre-traced axons. Our data suggest that this was mediated via specific cellular interactions of T cells and microglial cells since IFN-gamma alone was not sufficient
to induce axonal damage while such damage was apparent in response to TNF-alpha which is released by activated microglial cells. TNF-alpha secretion by both T cell
populations was negligible. Thus, MBP-specific T cells which invade nervous tissue in the course of neuroinflammation are more effective in axon-damaging recruiting microglial
cells than activated T cells of other specificities.
Important Points:
-Model: entorhinal/hippocampal slice culture
-IFN-gamma alone doesn't damage axons
-TNF-a damaged axons (released by activated microglia)
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