In actively demyelinating CNS lesions of multiple sclerosis (MS), proliferation of oligodendrocytes is a common feature and in established lesions, these cells are depleted. The present proposal is designed to test the hypothesis that oligodendrocytes can express interleukin-2 (IL-2) receptors, bind IL-2, express Class I and Class II MHC antigens, and be stimulated to proliferate by myelin breakdown products. Four approaches will be used to study these issues. Firstly, immunoelectron microscopy will be performed on MS lesions to determine if IL-2, IL-2 receptor and Class I and Class II MHC antigens can be demonstrated on the surface of the oligodendrocyte which will also be stained for galactocerebroside (GC) and myelin basic protein (MBP). Similar studies will be carried out on CNS lesions from Strain 13 guinea pigs with chronic relapsing experimental autoimmune encephalomyelitis (EAE), an experimental model which closely resembles MS and which displays entensive remyelination and oligodendroglial hyperplasia after treatment with a MBP-GC mixture. Secondly, to analyze further the factors responsible for the oligodendroglial hyperplasia seen in autoimmune demyelination and MS, oligodendrocyte cultures will be exposed to MBP or fragments of myelin to determine if myelin breakdown products have a mitogenic effect on these cells. Thirdly, to address the controversy of MHC antigen expression by oligodendrocytes, cultured oligodendrocytes of various ages from different strains of mice will be studied immunocytochemically for the presence of Class I and Class II MHC at the light and electron microscope levels. Fourthly, a similar study after exposure of the cultures to the lympholines, IL-2 and interferon- gamma, will examine the question of lymphokine induction of MHC on these cells. Thus, these studies should further delineate the role of the oligodendrocyte in the immunopathology of the MS lesion and factors important in the proliferation of this cell, a phenomenon important for remyelination. This information might be relevant to future therapeutic protocols in this disease.
| Moore, G R; Raine, C S (1988) Immunogold localization and analysis of IgG during immune-mediated demyelination. Lab Invest 59:641-8 |
