Dissociation of Antibody Production from Disease Suppression in the Inhibition of Allergic Encephalomyelitis by Myelin Basic Protein

Abstract

Normal guinea pigs challenged with a single injection of homologous myelin basic protein (BP) in Freund's complete adjuvant develop experimental allergic encephalomyelitis (EAE) and delayed hypersensitivity to BP but only rarely develop detectable circulating anti-BP antibodies. Treatment of guinea pigs with methotrexate before and during disease induction completely blocks EAE and suppresses delayed hypersensitivity to the homologous encephalitogenic BP. In contrast, animals treated with methotrexate for 19 days and sensitized after a 2-day time lapse develop the same intensity of EAE and delayed hypersensitivity to BP as those sensitized without prior methotrexate treatment. Treatment of guinea pigs with BP in incomplete adjuvant prior to encephalitogenic challenge suppresses development of both EAE and delayed hypersensitivity and simultaneously evokes anti-BP antibodies. Combined treatment of guinea pigs with methotrexate and BP prior to challenge almost completely suppresses the induction of anti-BP antibodies but does not interfere with the protective effect of the BP injections. Thus, the EAE-resistant state induced in guinea pigs by repeated injections of BP in incomplete adjuvant is apparently not dependent on induction of anti-BP antibodies. A more reasonable explanation for the resistance to EAE is that antigen accumulation prevents development or survival of a clone of BP-sensitized cells. These observations suggest that production or prevention of disease is correlated with induction or suppression of delayed hypersensitivity to BP and not with the presence or absence of circulating antibodies to BP. Antibodies to BP appear to be a coincidental phenomenon not involved in the pathogenesis of EAE.