Neuronal antigens modulate the immune response associated with experimental autoimmune encephalomyelitis

Abstract

Summary Rats primed with bovine myelin (BM) in complete Freunds adjuvant, develop acute experimental autoimmune encephalomyelitis (EAE). We have previously described that intraperitoneal administration prior to the active induction of the disease of a bovine synaptosomal fraction (BSF) and BM were effective ways of suppressing EAE. We found that both treatments diminish the incidence of the disease and reduced biochemical and histological alterations of the central nervous system (CNS). To characterize this suppression process, in this study we examined the antigen-specific immune response in animals protected from EAE. Lymph node mononuclear cells derived from sick EAE rats, as well as from those protected by BM and BSF, showed strong myelin basic protein (MBP) proliferation. Analysis of the humoral response against MBP showed a significant diminution of IgG2b anti-MBP titres in protected BM and BSF rats in contrast to sick EAE rats whose condition could be related to a diminished anti-MBP Th1 response. Finally, cells from rats protected by BSF and BM reduced the incidence of EAE when they were adoptively transferred into animals prior to active induction of the disease. These results suggest that a mechanism based on the generation of regulatory cells and immune deviation could account for the EAE suppression mediated by myelin as well as synaptosomal antigens.

Protective effect of a synapsin peptide genetically fused to the B subunit of Escherichia coli heat‐labile enterotoxin in rat autoimmune encephalomyelitis

“…These results clearly indicate that the genetic coupling of synapsin C domain to LTB constitutes a valid alternative model based probably on bystander suppression of immune response to a structurally unrelated antigen. The protective effect of LTBSC parallels the EAE suppression achieved by administration of a purified synaptosomal fraction (Degano et al, 1998, 2004).…”

“…A similar inverse relationship between susceptibility to EAE and level of anti‐MBP antibodies has been previously observed (Roth and Obata, 1991; Rivero et al, 1999). Th1‐like immune response has been associated in rats with the switching of secretion of immunoglobulins toward IgG2b, and the IgG1 isotype has been associated with a Th2‐like response (Mosmann and Sad, 1996; Rivero et al, 1999; Degano et al, 2004). Anti‐MBP IgG isotypes analysis showed that only animals orally treated with LTBSC had higher titers of IgG1.…”

“…These data prompted us to analyze the effect of intraperitoneal administration of a synaptosomal fraction given prior to the induction of acute EAE. This approach led to the suppression of the clinical signs and also reversed the expected CNS histological and biochemical alterations similarly to the suppression induced by treatment with myelin antigens (Degano et al, 1998, 2004).…”