Axonal damage induced by invading T cells in organotypic central nervous system tissue in vitro: Involvement of microglial cells

Neuroinflammation in the course of multiple sclerosis and experimental auto immune encephalomyelitis results in demyelination and, recently demonstrate d, axonal loss. Invading neuroantigen specific T cells are the crucial cell ular elements in these processes, Here we demonstrate that invasion of acti vated T cells induces a massive microglial attack on myelinated axons in en torhinal-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. C onversely, MBP-specific T cells displayed a significantly higher potential to trigger activation of microglial cells, i.e, upregulation of MHC class I I and ICAM-1 expression, and, most importantly, microglial phagocytosis of pre-traced axons, Our data suggest that this was mediated via specific cell ular interactions of T cells and microglial cells since IFN-gamma alone was not sufficient to induce axonal damage while such damage was apparent in r esponse to TNF-alpha which is released by activated microglial cells. TNF-a lpha secretion by both T cell populations was negligible, Thus, MBP-specifi c T cells which invade nervous tissue in the course of neuroinflammation ar e more effective in axon-damaging recruiting microglial cells than activate d T cells of other specificities.