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. 2006 Apr 5;10(3):365–377. doi: 10.1111/j.1750-3639.2000.tb00268.x

Axonal Damage Induced by Invading T Cells in Organotypic Central Nervous System Tissue in vitro: Involvement of Microglial Cells

Ulrike Gimsa 1,*,✉, Susanne VA Peter 1,*, Kathrin Lehmann 1, Ingo Bechmann 1, Robert Nitsch 1
PMCID: PMC8098590  PMID: 10885655

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‐γ. 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‐γ alone was not sufficient to induce axonal damage while such damage was apparent in response to TNF‐α which is released by activated microglial cells. TNF‐α 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.

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