November 18, 2009

Through brain tissue studies, scientists have known for a long time that the presence and activity of immune cells in the brain is a characteristic of MS. However, not much is known about how and why they are there. For instance, these cells need to cross the blood-brain barrier, a tight formation of blood vessel cells and cells surrounding the blood vessels that limits access to the brain. How they do this is not known.

However, a team of German scientists have now described part of this process, at least as it occurs in rats with the mouse model EAE. I encourage you to read the very interesting press release from the Max Planck Institute and watch the video from the experiment. They rigged a special optical camera to monitor the activities of fluorescently labeled T cells as they moved through blood vessels in the animal. The cells flowed normally in areas outside the brain, but when they got to the brain, some of the cells were seen to cling to the inside surface of the blood vessel. Furthermore, they began to "crawl" on the surface of the blood vessel, even going upstream, as if moving toward the source of a signal. After a while, some of the cells squeezed through the blood vessel walls into the brain. Once there, the T cells crawled again on the outside surface of the vessel until they touched a phagocyte (a type of cell that cleans up debris and can activate T cells). The scientists observed that many more T cells came through the barrier in locations where an inside T cell had made contact with a phagocyte -- indicating that the T cell had been activated and was sending out its own signals.

Finally, the team reported that MS antibody-based drugs (e.g., Tysabri) inhibited the crawling behavior of the T cells.

This type of imaging is something that could not ethically be done in humans, but it seems likely that the cellular behavior seen in this experiment is representative of what happens in other species as well. The team would next like to identify what signals guide the T cell behaviors (stopping, crawling, etc.) that they observed and potentially use this information to develop new MS treatments.