Suppression of experimental allergic neuritis by an antibody to the intracellular adhesion molecule ICAM-1.
Experimental allergic (autoimmune) neuritis (EAN) was induced in Lewis rats either by inoculation with bovine spinal root myelin or injection of neuritogenic P2-specific T cells. Injection of a purified monoclonal antibody (1A-29) to the intercellular adhesion molecule-1 (ICAM-1) prevented or transiently suppressed myelin-induced EAN depending on the timing of antibody application. Administration of 1A-29 suppressed moderate adoptive transfer EAN (AT-EAN) but not severe AT-EAN. In contrast, treatment with phosphate buffered saline or an unrelated IgG1 had no effect on the course of the disease. Histological sections of the peripheral nervous system (PNS) showed a marked reduction of inflammatory infiltrates and perivascular demyelination in rats injected with 1A-29. The effect of 1A-29 on the concanavalin A (Con A)- and P2-dependent proliferation of neuritogenic P2-specific T cells was studied in vitro. Our data suggest that antibodies to ICAM-1 act on the induction and effector phase of the immune response by inhibiting both early interactions between immunocompetent cells after exposure to foreign antigen and transendothelial migration of primed T cells into the peripheral nerve. Treatment with antibodies to leucocyte adhesion molecules could be a useful therapeutic approach to autoimmune disease of the PNS.
Archelos
J J
JJ
Department of Neurology, Julius-Maximilians-Universität Würzburg, Germany.
Mäurer
M
M
Jung
S
S
Toyka
K V
KV
Hartung
H P
HP
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D015815:Cell Adhesion Molecules / Q000276:immunology*; D002455:Cell Division / Q000187:drug effects; D003208:Concanavalin A / Q000494:pharmacology; D005260:Female; D007074:Immunoglobulin G / Q000627:therapeutic use; D016219:Immunotherapy, Adoptive; D018799:Intercellular Adhesion Molecule-1; D004676:Myelin Basic Protein; D018996:Myelin P2 Protein; D009444:Neuritis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D010525:Peripheral Nerves / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000637:transplantation
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D007074:Immunoglobulin G; D004676:Myelin Basic Protein; D018996:Myelin P2 Protein; D003208:Concanavalin A; D018799:Intercellular Adhesion Molecule-1