Role of the leukocyte-adhesion molecule L-selectin in experimental autoimmune encephalomyelitis

L-selectin is an adhesion molecule expressed on T cells and monocytes. It mediates rolling - the initial step of transendothelial migration. In this study, we investigated the role of L-selectin in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. EAE was induced in Lewis rats by active sensitization with myelin basic protein (MBP-EAE), or by adoptive transfer using MBP specific T cells (AT-EAE). Treatment with HRL3, a monoclonal antibody to L-selectin, and its F(ab')(2) fragments efficiently suppressed MBP-EAE, and had a mild inhibitory effect on AT-EAE. Histological examination revealed a marked reduction of inflammatory infiltrates after treatment with HRL3. Administration of the control antibody HRL4 did not significantly alter the course of the disease. HRL3 caused T-cell depletion in the draining lymph nodes and spleen and a downregulation of L-selectin expression on T cells. We conclude that L-selectin-dependent mechanisms are involved in the pathogenesis of EAE. Modulation of L-selectin in vivo by antibodies or by competitive antagonists could be a novel therapeutic approach to autoimmune diseases of the central nervous system. (C) 1998 Elsevier Science B.V. All rights reserved.