[A view for understanding the pathogenesis of multiple sclerosis].

There are 2 hypotheses for understanding the pathogenesis of multiple sclerosis (MS), viral and autoimmune ones. Although antibodies to many viruses are elevated, an MS-specific virus has not been found and none of conventional viruses has been definitely located in MS lesions. Thus, viruses, if involved, seem to be indirect. Autoimmune encephalomyelitis (EAE) has represented main aspects of MS such as inflammatory demyelinating plaques, spontaneous onset, remission and relapse. This was proven by transgenic mice that express T cell receptor genes of myelin basic protein (MBP)-specific encephalitogenic T cells (Goverman et al, 1993). The animals developed spontaneous EAE and relapsed when kept in the conventional condition. Otherwise, it was necessary to inject bacterial antigens, when they were kept in an SPF condition. We have shown that MBP89-101 specific encephalitogenic T cell clones are polyreactive (Kozovska et al, submitted). In MS, T cell responses to MBP and proteolipid protein (PLP) have been studied and certain T cell immunodominant regions are suggested. Some of the MHC-class II-restricted and MBP peptide-specific T cell clones responded to several viral antigens (Wucherpfenning and Strominger, 1995). Thus, it is highly probable that autoaggressive T cells are polyreactive and activated by viral and other antigens. I believe that this is the central mechanism operating in MS. Before reaching this conclusion, we must show that the MBP- or PLP-specific polyreactive T cells are indeed encephalitogenic. In order to prove this, we must establish an animal model, humanized mice.