INHIBITION OF EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS BY AN ANTIBODY TO THE INTERCELLULAR-ADHESION MOLECULE ICAM-1

Experimental autoimmune encephalomyelitis (EAE) was induced in Lewis r ats by active immunization with myelin from guinea pig spinal cord by the encephalitogenic myelin basic protein or by adoptive transfer usin g myelin basic protein-specific CD4-positive T cells. Treatment with p urified monoclonal antibody (1A-29) to the intercellular adhesion mole cule-1 and its F(ab')2 fragments efficiently suppressed active EAE. Co ntrol treatment with an irrelevant antibody or saline did not alter th e course of the disease. Histological sections of the central nervous system showed a pronounced reduction of inflammatory infiltrates durin g treatment with antibody to intercellular adhesion molecule-1. In the adoptive transfer model of EAE, 1A-29 had only a minor effect. Prolif eration assays on lymph node cells ex vivo from 1A-29- and saline-trea ted animals were performed. Administration of 1A-29 suppressed antigen -specific T-cell proliferation. The differential effects in EAE versus adoptive transfer EAE suggest that 1A-29 acts predominantly on the in duction phase of the immune response and, to a lesser extent, on the t ransendothelial migration of T cells. We conclude that intercellular a dhesion molecule-1-dependent pathways are critically involved in the p athogenesis of EAE and that antibodies to leukocyte adhesion molecules could be a novel therapeutic approach to autoimmune disease of the ce ntral nervous system.