Demyelinating experimental allergic encephalomyelitis (EAE) in the rat: treatment with a monoclonal antibody against activated T cells.
We used a new version of experimental autoimmune encephalomyelitis (EAE) in the rat to investigate immunotherapy of demyelination during autoimmune disease of the central nervous system (CNS). Encephalitis was induced by immunization of rats with myelin basic protein (MBP), and demyelination by systemic injection of a monoclonal antibody, 8-18C5, specific for a myelin/oligodendrocyte glycoprotein (MOG). Antibody injection resulted in hyperacute disease progression and extensive demyelination throughout the CNS. Immunotherapy of antibody-induced demyelination was possible with another monoclonal antibody, pta-3, specific for activated rat T cells. These findings demonstrate the synergy of T cell-mediated and antibody-dependent processes in rat CNS demyelination in vivo. Histologically, immunotherapy reduced the numbers of meningeal mononuclear cell inflammatory foci, but not parenchymal inflammation in the early phase of demyelinating disease. Animals which had received pta-3 antibody had less inflammation than untreated rats in the convalescent phase. Multiple pta-3 treatments most effectively suppressed inflammation. Furthermore, antibody-treated rats with demyelination developed a series of neurologic signs, including pronounced spasticity; that were not observed in control EAE rats and thus appears to be associated with the demyelinating process.
Schluesener
H J
HJ
Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115.
Sobel
R A
RA
Weiner
H L
HL
D000208:Acute Disease; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001921:Brain / Q000473:pathology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D005620:Freund's Adjuvant; D007963:Leukocytes, Mononuclear / Q000473:pathology; D008213:Lymphocyte Activation; D004676:Myelin Basic Protein; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D004676:Myelin Basic Protein; D005620:Freund's Adjuvant