Effector T cell interactions with meningeal vascular structures in nascent autoimmune CNS lesions

T cells in autoimmunity A two-photon fluorescence microscopy study of rats with experimental autoimmune encephalomyelitis — a model for multiple sclerosis — shows autoimmune-disease-triggering blood T cells first directly attaching and then scanning the internal surface of the spinal meningeal vasculature, sometimes crawling against the direction of blood flow. Once across the blood–brain barrier, the T cells engage with antigen-presenting phagocytes that in turn stimulate their further differentiation and tissue infiltration. The structures involved in these interactions with T cells could be potential candidate targets for therapy against autoimmune brain disease. The tissues of the central nervous system are shielded from the blood circulation by specialized vessels, impermeable to cells and most circulating macromolecules. Despite this, central nervous system tissues are subject to immune surveillance and are vulnerable to autoimmune attack. Here, intravital two-photon imaging is used to observe, in real-time, the interactive processes between effector T cells and cerebral structures leading to an experimental rat model of autoimmune encephalitis. The tissues of the central nervous system are effectively shielded from the blood circulation by specialized vessels that are impermeable not only to cells, but also to most macromolecules circulating in the blood. Despite this seemingly absolute seclusion, central nervous system tissues are subject to immune surveillance and are vulnerable to autoimmune attacks 1 . Using intravital two-photon imaging in a Lewis rat model of experimental autoimmune encephalomyelitis, here we present in real-time the interactive processes between effector T cells and cerebral structures from their first arrival to manifest autoimmune disease. We observed that incoming effector T cells successively scanned three planes. The T cells got arrested to leptomeningeal vessels and immediately monitored the luminal surface, crawling preferentially against the blood flow. After diapedesis, the cells continued their scan on the abluminal vascular surface and the underlying leptomeningeal (pial) membrane. There, the T cells encountered phagocytes that effectively present antigens, foreign as well as myelin proteins. These contacts stimulated the effector T cells to produce pro-inflammatory mediators, and provided a trigger to tissue invasion and the formation of inflammatory infiltrations.