Speakers
Description
A common feature of inflammatory CNS diseases such as multiple sclerosis, rasmussen encephalitis, neuromyelitis optica or the Susac syndrome represents the transmigration of autoreactive T cells through the brain endothelial cell layer into the CNS, where they can cause tissue destruction and neuronal loss.
With this project we are aiming to investigate the molecular mechanisms of immune cell and endothelial cell interaction in different CNS inflammatory diseases. While previous studies mainly focused on immune cell changes, we are examining the consequences on endothelial cells due to the interaction with CD8+ T cells. While above mentioned diseases are presumably antigen driven, however how and where T cells get (re)-activated in close proximity to the CNS is not quite clear.
Our data suggest that primary mouse brain microvascular endothelial cells (MBMECs) can present antigen on their surface via the MHC class I receptor and therefore are able to activate naïve antigen specific T cells. Coculture of naïve OT1 T cells with SIINFEKL loaded endothelial cells results in a rapid reduction in endothelial barrier function as illustrated by a reduced transendothelial electrical resistance (TEER) and increased permeability to soluble molecules.
The antigen specific interaction of endothelial cells with T cells caused an upregulation of MHC class I expression as well as an increase in key adhesion molecules such as ICAM and VCAM on the endothelial cell side. In order to cause endothelial cell damage a direct cell – cell contact seems necessary. Despite strong impairment of EC barrier integrity, T cells did not elicit apoptosis in endothelial cells.
Taken together, these data could identify novel antigen-dependent reciprocal interactions between brain endothelial cells and T cells with future implications for CNS inflammatory diseases.
