Interaction of astrocytes and newly formed oligodendrocytes in resolving multiple sclerosis lesions

Cells resembling oligodendrocytes are sometimes seen within reactive astrocytes in fresh lesions in multiple sclerosis. Using immunostained paraffin and epoxy sections of fresh plaques obtained at autopsy from a series of cases of short clinical duration, it was found that small cells with round nuclei are commonly observed within reactive astrocytes in some hypercellular plaques and that these cells are phenotypically undifferentiated oligodendrocytes, i.e., nonmyelinating cells expressing intensely the oligodendrocyte determinants 2',3'-cyclic nucleotide 3'-phosphohydrolase and the carbohydrate epitope present on the family of cell adhesion molecules recognized by monoclonal antibody HNK-1. They also stain positively for IgG. This unusual astrocyte-oligodendrocyte interaction, which appears to be restricted to nonmyelinating oligodendrocytes in lesions of several weeks' to several months' duration, has not been described during normal oligodendrocyte differentiation or in experimental central remyelinating lesions. It bears some resemblance, however, to a pattern of slow oligodendrocyte destruction seen previously in organotypic perinatal central nervous tissue cultures exposed to multiple sclerosis serum. It is concluded that the evolution of some multiple sclerosis lesions early in the course of the disease is associated with abnormal binding and/or destruction of newly generated oligodendrocytes by reactive astrocytes. These observations raise new questions concerning mechanisms underlying failed remyelination in multiple sclerosis, including the novel possibility of an immune response directed against a developmentally restricted oligodendrocyte antigen.