T cells that recognize the "self", known as autoreactive T cells, can infiltrate the central nervous system (CNS) and cause disorders like multiple sclerosis. Using a rat model of multiple sclerosis, Marija Pesic and colleagues use a microscopy technique, two-photon imaging, to track T cells as they interact with the blood brain barrier to enter the CNS and become activated upon contact with an antigen. This image shows the leptomeningeal blood vessels in red with the green T cells crawling (left) and rolling (right) through the vessels. You can watch videos of the T cells as they move through the vessels here and here. These experiments provide a picture of how the immune system interacts with the CNS during autoimmune disease.
Autoreactive T cells can infiltrate the CNS to cause disorders such as multiple sclerosis. In order to visualize T cell activation in the CNS, we introduced a truncated fluorescent derivative of nuclear factor of activated T cells (NFAT) as a real-time T cell activation indicator. In experimental autoimmune encephalomyelitis, a rat model of multiple sclerosis, we tracked T cells interacting with structures of the vascular blood-brain barrier (BBB). 2-photon imaging documented the cytoplasmic-nuclear translocation of fluorescent NFAT, indicative of calcium-dependent activation of the T cells in the perivascular space, but not within the vascular lumen. The activation was related to contacts with the local antigen-presenting phagocytes and was noted only in T cells with a high pathogenic potential. T cell activation implied the presentation of an autoantigen, as the weakly pathogenic T cells, which remained silent in the untreated hosts, were activated upon instillation of exogenous autoantigen. Activation did not cogently signal long-lasting arrest, as individual T cells were able to sequentially contact fresh APCs. We propose that the presentation of local autoantigen by BBB-associated APCs provides stimuli that guide autoimmune T cells to the CNS destination, enabling them to attack the target tissue.
Marija Pesic, Ingo Bartholomäus, Nikolaos I. Kyratsous, Vigo Heissmeyer, Hartmut Wekerle, Naoto Kawakami