Encephalitogenic T cells on their way through blood-brain barrier and CNS tissue

Fig. 5. T cell crawling on vascular lumen are not activated. Left: 3D reconstructed picture of MBP specific T cell with GFP tag crawling in luminal surface. Right: expressing ΔNFAT-GFP exclusively in cytoplasm (green ring).

Using intravital two-photon microscopy, we retrace the entire invasion process of MBP specific T cells (TMBP cells) into the CNS. Low numbers of pioneer TMBP cells arrived in the leptomeningeal vessels on day 1 after transfer. More TMBP cells appeared in the following hours and actively crawled inside the blood vessels, often against the blood stream (Fig. 5). This intraluminal crawling was prevalent for the leptomeningeal tissue, while classical rolling was dominant in vessels of peripheral organs. Anti-integrin alpha4 antibody, as used for treatment of human MS (Natalizumab), abolished intraluminal crawling within a few minutes after injection.Following intraluminal crawling, T cells pass through the vascular wall and continue migrating along the abluminal surface of the vessels. A substantial part of T cells established contacts with local antigen presenting cells (APCs).

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