Interaction of α4-integrin with VCAM-1 is involved in adhesion of encephalitogenic T cell blasts to brain endothelium but not in their transendothelial migration in vitro

Based on the observation that antibodies directed against alpha 4-integrin and its counterreceptor VCAM-1 inhibit inflammatory cell recruitment into the central nervous system (CNS) during experimental autoimmune encephalomyelitis (EAE), it has been concluded that alpha 4-integrin/VCAM-1 interaction plays a critical role in T cell interaction with the blood-brain barrier (BBB) endothelium. in order to define the exact role of alpha 4-integrin and VCAM-1 in T cell recruitment across the BBB endothelium we set up in vitro studies, where we investigated the interaction of freshly activated autoaggressive T cell blasts with the brain endothelial cell line bEnd5. A large panel of blocking antibodies directed against the alpha 4-, beta 1- and beta 7-integrin subunits or against the alpha 4 beta 7-heterodimer and against endothelial VCAM-1 significantly reduced adhesion of encephalitogenic T cell blasts to brain endothelium. However, the very same antibodies did nor influence transendothelial migration of autoaggressive T cell blasts across a bEnd5 monolayer. Our in vitro observations, therefore, suggest that in vivo alpha 4/VCAM-1 interactions are not involved in transendothelial migration of encephalitogenic T cells across the BBB but rather mediate earlier steps of T cell/BBB-interaction such as firm adhesion. (C) 2000 Elsevier Science B.V. All rights reserved.