Watching T cells cross the blood-brain barrier

A recent press release by the Max Planck Institute for Neurobiology in Martinsried reports on a paper (‘Effector T cell interactions with meningeal vascular structures in nascent autoimmune CNS lesions’, Nature 462, 94) where detailed information is given on certain aspects of the way that activated T cells cross the blood-brain barrier during the development of the disease EAE in rats. In fact the authors were able to film the behaviour of the cells in living rats over extended time periods. In the best-known type of interaction between white blood cells and blood vessels through which they pass, the cells roll along the wall of the vessels until at some point they stop and exit the vessel by squeezing between the cells forming the wall. In this work the disease is provoked by introducing activated T cells which recognize myelin basic protein. In the case of most blood vessels they roll as just described but in the case of certain blood vessels belonging the BBB they instead crawl along the walls, often against the direction of the blood flow. This type of behaviour has apparently not been seen before in T cells although it is known from some other types of leukocytes. It looks as if the cells are searching for something particular although it is not clear what. Some of them eventually cross the BBB into the central nervous system while others let go and return to the bloodstream.

Once the cells get into the CNS they encounter phagocytic cells which activate them and cause them to produce substances such as interferon and interleukin 17. This then causes further T cells to be recruited to the CNS, thus leading to the full development of the disease. The identity of these phagocytic cells seems a bit mysterious. They are described in the paper as being intermediate between macrophages and dendritic cells. They are said to be constantly probing the region just outside the vessel walls. What I find particularly interesting about this work is that instead of just obtaining indirect information on what is going on it shows very directly what the cells are doing. The information presented in the paper is much more extensive that what I have just indicated. It has been possible to follow the cells on their way to deeper levels of the brain and to compare these particular T cells to other activated T cells which recognize a different antigen having nothing to do with CNS tissue.

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