Role of glucocorticioids on T cell recruitment across the blood-brain barrier

Journal/Book: Z Rheumatol 1999; 58: 296. 1999;

Abstract: B. Engelhardt; W. G. Kerckhoff-Institut Max-Planck-Institut für physiologische und klinische Forschung Bad Nauheim Until recently the central nervous system (CNS) has been considered to be an immunologically privileged site where no immunosurveillance and hence no lymphocyte traffic occurs. This theory was in part supported by the fact that the CNS is able to exclude components of the immune system via the highly specialized vascular blood-brain barrier (BBB). It has become evident however that during a wide range of inflammatory diseases in the CNS mononuclear cells readily gain access to the CNS parenchyme and that immunological mechanisms are intimately involved in the pathogenesis of these diseases. The prototype model for human inflammatory demyelinating diseases of the CNS such as multiple sclerosis (MS) is experimental autoimmune encephalomyelitis (EAE). In EAE autoaggressive CD4+ T cells gain access to the CNS and cause edema inflammation and demyelination within the CNS white matter. As endothelial cells actively participate in the regulation of lymphocyte entry into various tissues it is to be expected that the specialization of the BBB endothelium extends to CNS-specific traffic signals for lymphocytes. In fact we have demonstrated that expression of E- and P-selectin is suppressed on BBB endothelium by factors derived from the CNS microenvironment and that E- and P-selectin are not involved in the recruitment of inflammatory cells across the BBB. In contrast we could show by the in vivo application of a large panel of monoclonal antibodies (mAbs) directed against a4-integrins and VCAM-1 that a4/VCAM-1 interaction plays a crucial role in T cell interaction with the BBB endothelium. In vitro studies demonstrated that a4/VCAM-1 mediated interaction of T cells with brain endothelium is involved in their adhesion to brain endothelium but not in their transendothelial migration. ... le

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