Experimental autoimmune encephalomyelitis: Antigen-induced inhibition of biochemical and immunohistological alterations

Abstract

A comprehensive biochemical, immunological, and histological study was undertaken during suppression of experimental autoimmune encephalomyelitis (EAE) induced by antigen‐specific inhibition of the immune response. Pretreatment of Wistar rats by intraperitoneal administration of low doses of saline‐soluble bovine myelin or myelin basic protein (MBP) but not with ovalbumin suppresses the appearance of the clinical symptoms of EAE induced by sensitization with bovine myelin in complete Freund's adjuvant. Analysis of the central nervous system (CNS) of animals pretreated with MBP or whole myelin shows inhibition of the diminution of MBP and 2′,3′‐cyclic nucleotide 3′‐phosphohydrolase (CNPase) activity observed in the EAE animals or in rats pretreated with ovalbumin. With respect to the CNS lipid content, these suppressive treatments abolish the increase in esterified cholesterol and partially revert the diminution in the content of cerebrosides and total cholesterol characteristic of the acute stage of the disease. Concomitantly, meningeal and parenchymal infiltration with mononuclear cells and deposits of immunoglobulins in the infiltrated regions as well as in spinal cord motor neurons were reduced. Analysis of the humoral response to myelin antigens shows that all EAE as well as treated animals developed antibodies to MBP and other myelin proteins. However, a higher incidence and level of these antibodies was observed in nontreated EAE animals and MBP‐ and ovalbumin‐treated rats, while rats treated with total bovine myelin showed a highly reduced humoral response. The present results indicate that intraperitoneal treatment with soluble forms of myelin antigens, concomitant with the suppression of the clinical symptoms of the disease, markedly reduces the biochemical and histological alterations occurring in EAE animals and produces changes in the autoimmune humoral response. © 1996 Wiley‐Liss, Inc.

Neuronal antigens modulate the immune response associated with experimental autoimmune encephalomyelitis

“…This treatment markedly diminished the incidence of paralysis and reduced the characteristic changes in some CNS components observed during the acute period of the disease. Therefore, this treatment is an effective way of suppressing EAE in a similar form to the suppression mediated by myelin antigens shown previously 12 , 13 . As mentioned above, we did not detect contamination of the BSF with myelin proteins.…”

“…As expected, a strong reaction is apparent at the level of MBP in the BM fraction but is not observed in the BSF fraction. This immunoassay with specific antiserum is a sensitive method that can detect about 1 ng of antigen 12 . Consequently, in assays using up to 100 µg of BSF proteins, if contamination of MBP in the BSF of about 1:100 000 had of occurred, we should have detected it.…”

“…Complete Freund's adjuvant, Con A, BSA, RPMI 1640 medium, Histopaque 1083, monoclonal mouse antirat IgG2a antibody, antirat IgG2b antibody, antirat IgG1 antibody, HRP‐conjugated antimouse IgG, HRP‐conjugated antimouse IgM and HRP‐conjugated goat antirat immunoglobulins were all supplied by Sigma‐Aldrich (St Louis, MO, USA). Mouse anti‐MBP monoclonal antibody (MAb BP1.3G9) was from Eurogenetics (Tessenderlo, Belgium) and rabbit anti‐MBP antiserum was prepared and used as described by De Santis & Roth 11 and Degano et al 12 . Synapsin I and rabbit antisynapsin I affinity‐purified antibody were from Signal Transduction (San Diego, CA, USA) and [Methyl‐ 3 H] thymidine ([ 3 H]TdR) was from NEN Life Science Products, Inc. (Boston, MA, USA).…”

“…We have previously shown that i.p. administration of low doses of saline soluble bovine myelin (BM) or MBP, but not ovalbumin, markedly reduce the incidence and severity of clinical symptoms and abrogate the histological and biochemical alterations observed in CNS tissue of Wistar rats with EAE 12 , 13 . Considering the described immunological cross‐reaction between myelin and synaptosomal antigens, we studied whether the i.p.…”