T cell migration into the central nervous system during health and disease: Different molecular keys allow access to different central nervous system compartments

<jats:title>Abstract</jats:title><jats:p>Central nervous system (CNS) homeostasis is a prerequisite for the proper communication of neuronal cells. To this end, the endothelial blood–brain barrier (BBB) and the epithelial blood–cerebrospinal fluid barrier (BCSFB) tightly seal off the CNS from the continuously changing milieu within the blood stream. It is now well established that despite the presence of these barriers, the CNS is subject to immune surveillance and immune mediated pathogenic events. Numerous studies in an animal model for multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), have elucidated that memory T cells can cross the non‐inflamed BBB or BCSFB using specific molecular keys and gain access to the cerebrospinal fluid (CSF) drained ventricular, subarachnoidal and perivascular spaces. If these pioneer T cells encounter their specific antigen on antigen presenting cells strategically localized immediately behind the brain barriers, reactivation of the T cells will trigger a local inflammatory response, leading to the stimulation of the BBB. The activated BBB will then provide novel traffic signals allowing for the entry of large numbers of circulating inflammatory cells into the perivascular spaces and finally across the glia limitans into the CNS parenchyma, where they progress to initiate tissue injury. (Clin. Exp. Neuroimmunol. doi: 10.1111/j.1759‐1961.2010.00009.x, May 2010)</jats:p>