Differential DM20 mRNA expression distinguishes two distinct patterns of spontaneous recovery from murine autoimmune encephalomyelitis

Experimental autoimmune encephalomyelitis (EAE) is an animal model for mult iple sclerosis (MS) mediated by T cells responding to CNS myelin proteins. Immunization of SWXJ mice with the immunodominant p139-151 peptide of myeli n proteolipid protein (PLP) results in a relapsing-remitting pattern of EAE characterized by incomplete remyelination during clinical recovery. In the present study we observed two distinct clinical patterns of spontaneous re mission during recovery from EAE, viz., sustained remission involving conti nuous neurologic improvement and aborted remission involving modest transie nt clinical improvement. We hypothesized that the ability to recover from a utoimmune demyelination was directly linked to remyelination events that re capitulated developmental processes. Quantitative immunocytochemistry of CN S tissue showed decreased demyelination in mice undergoing sustained remiss ion compared to mice undergoing aborted remission. Quantitative RT-PCR anal ysis showed elevated expression of DM20, the developmental isoform of PLP, in CNS tissue from mice undergoing sustained remission compared to mice und ergoing aborted recovery. Moreover, DM20 expression was similarly elevated in CNS tissue from mice undergoing sustained recovery from EAE relapse. Our data indicate that expression of the developmental DM20 isoform of PLP is intimately associated with decreased demyelination and sustained clinical r ecovery from EAE, Thus, DM20 gene expression may provide an appropriate mol ecular target for promoting CNS remyelination and may serve as a useful mar ker for predicting clinical outcome and assessing the effectiveness of stra tegies aimed at promoting CNS tissue repair during autoimmune demyelinating disease. (C) 2001 Wiley-Liss, Inc.