ABSTRACT

Oligodendrocytes (OLs) and their myelin membranes are considered to be the primary targets of the immune-mediated injury that is postulated to underlie the pathogenesis of the multiple sclerosis (MS) disease process. 1,2 Such selective susceptibility could be determined by the properties of either the effector or target side of the immune response. The results of immunohistochemical and in situ hybridization based analyses indicate that there is heterogeneity with regard to the cellular and humoral immune mediators present in MS lesions. 3 Furthermore, there is preliminary data that individual cases of MS can be categorized into distinct immunopathological phenotypes. If so, this would imply that different immune effector mechanisms are operative in individual cases. Counterparts of each of the distinct MS lesion phenotypes are recognized in the various models of experimental autoimmune encephalomyelitis (EAE) that have been created. 4,5

Defining the precise molecular mechanisms that can result in immune-mediated injury of OLs or myelin should provide opportunities to develop therapeutic strategies directed at both the effectors and the targets of this process. One approach to this challenge is to evaluate the functional interactions between immune effector cells and molecules with resident central nervous system (CNS) cells in vitro. Methods now exist to establish highly enriched cultures of the various glial cells that are resident in the CNS. In our own studies, we have used tissues that have been resected from the adult human CNS during the course of surgery to alleviate intractable epilepsy, to prepare dissociated cultures of OLs. When possible, we have attempted to corroborate our in vitro observations regarding the molecular properties of the immune mediators and the OL targets with in vivo observations.