Suppression and Treatment of Chronic Relapsing Experimental Allergic Encephalomyelitis

Abstract

AbstractChronic relapsing experimental allergic encephalomyelitis (EAE) in inbred Strain 13 guinea pigs, a laboratory model highly reminiscent of multiple sclerosis (MS) clinically, pathologically and immunologically, has been applied to therapeutic problems of relevance to MS. Suppression of this model with myelin basic protein (MBP), the major encephalitogenic determinant of central nervous system (CNS) myelin, has proven highly successful in experiments in which MBP was administered prior to the onset of disease. However, treatment with the same regimen of MBP injections after the onset of disease was less successful. Some stabilization of the disease course was noted and although relapses were not prevented, they were lessened in severity. On the basis of previous work implying that in EAE, MBP might serve to recruit T cells to the CNS while galactocerebroside (GC), a major glycolipid of CNS myelin, might be responsible for the B cell (antibody) component of the immune response (the putative demyelinating component), a group of guinea pigs with chronic relapsing EAE has been treated with a combination of MBP and GC. Preliminary findings indicate a marked clinical improvement in MBP/ GC-treated animals over similar animals given MBP alone. CNS lesions in MBP/GC-treated animals displayed an overabundance of oligodendrocytes and widespread remyelination. There was no lesion progression and an absence of lymphocytes was noted. Lymphocyte findings in MBP- and MBP/GC-treated animals have demonstrated a significant increase in suppressor T cells shortly after the commencement of treatment. Lymphocyte labelling in situ has revealed that T cells appear first in the CNS and assume a parenchymal distribution and B cells arrive later and remain meningeal and perivascular. In treated groups, lymphocytes were rare in the CNS and appeared to have been prevented from entering the tissue. The present, preliminary findings have shown that MBP/GC is a ) more effective than MBP alone in treating chronic relapsing EAE, b ) prevents lesion progression, c ) promotes CNS repair and d ) allows for some return of function.