A truly amazing paper in today’s Nature1 shows 2-photon microscopy videos of T cells entering the brain in search of their target antigen.  The title of this post is taken from the commentary,2 also in Nature.

Disease-causing T cells first adhere to the inner walls of the pial vessels and then crawl in continuous contact with activated endothelial cells, most often in the opposite direction to the blood flow. …  After crossing the blood-vessel wall, the lymphocytes move along the outer surface of the vessel, encountering an array of antigens displayed by antigen-presenting cells, including macrophages. …  Last, the cells detach from the outer surface of the blood vessel and enter the spinal cord, travelling most often alongside penetrating vessels. In the spinal cord, they initiate tissue injury.2

There are a myriad of stunning videos and images.  Here’s just one video of the many, showing T cells (in green) exiting a blood vessel in the brain, and (in part 1) swimming off into the brain tissue to spread devastation and destruction (since these are autoimmune, self-reactive T cells):

The videos show TMBP-GFP cells (green) extravasating from leptomeningeal blood vessels (red) at day 2 (1st part) or day 2.5 (2nd part) p.t. Z-projections and 3D reconstruction is depicted (1st part, right). 3D reconstruction was performed using Imaris software. The 2nd part shows three extravasation events (arrows). Recording time, 37 min and 30 min, respectively. 1

  1. Bartholomäus, I., Kawakami, N., Odoardi, F., Schläger, C., Miljkovic, D., Ellwart, J., Klinkert, W., Flügel-Koch, C., Issekutz, T., Wekerle, H., & Flügel, A. (2009). Effector T cell interactions with meningeal vascular structures in nascent autoimmune CNS lesions Nature, 462 (7269), 94-98 DOI: 10.1038/nature08478[][]
  2. Ransohoff, R. (2009). Immunology: In the beginning Nature, 462 (7269), 41-42 DOI: 10.1038/462041a[][]