Juan J. Archelos, Bernd C. Kieseier, Hans-Peter Hartung
Multiple Sclerosis Research Group, Department of Neurology, Karl-Franzens-Universität, Graz, Austria

Under physiological conditions the blood-brain barrier (BBB) constitutes a major anatomical impediment to macromolecules and cells. In immune-mediated disorders of the central nervous system (CNS) such as multiple sclerosis (MS) or experimental autoimmune encephalomyelitis (EAE) perivascular accumulation of immune cells is a classical histopathological feature. Mechanisms that are operative in transendothelial migration of T cells and monocytes have been elaborated in vitro and in animal models of MS. Obviously, lymphocytes mutually interact with endothelial cells at the BBB which enables them to invade the CNS and initiate a local inflammation with subsequent demyelination. Distinct classes of adhesion molecules (AM) such as integrins, selectins and members of the immunoglobulin-superfamily on both endothelial cells and T cells play a critical role in this central pathogenetic process. Their dynamic sequential expression on both interacting cell types at the BBB directs and controls immune cell migration. In addition to AM, chemokines have been demonstrated to be crucial for T cell recruitment into the CNS during inflammation.The important functional role of these molecules in the pathogenesis has been elucidated in treatment studies in EAE. These clearly show a significant reduction of clinical signs and histopathological changes after functional blockade of certain AM or chemokines. The clinical value of this treatment approach that aims at inhibiting transendolthelial migration of immune cells in MS is currently under investigation.