Analysis of humoral and cellular events and the role of lipid haptens during CNS demyelination.

Abstract

In recent years, considerable interest has focused on the possibility that in experimental allergic encephalomyelitis (EAE), antigen other than myelin basic protein (MBP) may be required for the initiation of demyelination and for the development of exacerbating-remitting disease. Previous results from these laboratories have implicated a role for antibodies against galactocerebroside (GC) in initiating demyelination of central nervous system (CNS) tissue in vitro (8) and in vivo (9). We have now used the rabbit eye model to dissect further the role of antibodies in causing CNS demyelination. The results show: that in animals directly sensitized against GC, no spontaneous CNS lesion develops but primary demyelination is observed if a mononuclear inflammatory reaction is superimposed; that in rabbits sensitized against MBP, antiserum against GC causes enhanced demyelination; and that in normal animals, anti-GC serum initiates primary demyelination only when an inflammatory reaction is induced by supernatants of activated lymphocytes. Injection of anti-GC serum alone has no pathologic effect. These results suggest that antibodies against lipid haptens are capable of causing primary demyelination in the CNS in vivo but that effector cells provided by an inflammatory response are required. Thus, the development of the fully demyelinating lesion probably depends on both cellular and humoral mechanisms.