Inhibition of experimental autoimmune encephalomyelitis by an antibody to the intercellular adhesion molecule ICAM-1.
Experimental autoimmune encephalomyelitis (EAE) was induced in Lewis rats by active immunization with myelin from guinea pig spinal cord by the encephalitogenic myelin basic protein or by adoptive transfer using myelin basic protein-specific CD4-positive T cells. Treatment with purified monoclonal antibody (1A-29) to the intercellular adhesion molecule-1 and its F(ab')2 fragments efficiently suppressed active EAE. Control treatment with an irrelevant antibody or saline did not alter the course of the disease. Histological sections of the central nervous system showed a pronounced reduction of inflammatory infiltrates during treatment with antibody to intercellular adhesion molecule-1. In the adoptive transfer model of EAE, 1A-29 had only a minor effect. Proliferation assays on lymph node cells ex vivo from 1A-29- and saline-treated 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 induction phase of the immune response and, to a lesser extent, on the transendothelial migration of T cells. We conclude that intercellular adhesion molecule-1-dependent pathways are critically involved in the pathogenesis of EAE and that antibodies to leukocyte adhesion molecules could be a novel therapeutic approach to autoimmune disease of the central nervous system.
Archelos
J J
JJ
Department of Neurology, Julius-Maximilians-Universität, Würzburg, Germany.
Jung
S
S
Mäurer
M
M
Schmied
M
M
Lassmann
H
H
Tamatani
T
T
Miyasaka
M
M
Toyka
K V
KV
Hartung
H P
HP
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D001921:Brain / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D007140:Immunoglobulin Fab Fragments / Q000627:therapeutic use; D018799:Intercellular Adhesion Molecule-1; D008297:Male; D004676:Myelin Basic Protein; D009186:Myelin Sheath; D051381:Rats; D011917:Rats, Inbred Lew; D013116:Spinal Cord / Q000473:pathology; D013601:T-Lymphocytes
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D007140:Immunoglobulin Fab Fragments; D004676:Myelin Basic Protein; D018799:Intercellular Adhesion Molecule-1