IMMUNE TOLERANCE MEDIATED BY RECOMBINANT PROTEOLIPID PROTEIN PREVENTSEXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS

Proteolipid protein (PLP), a transmembrane protein expressed only in t he central nervous system (CNS), is a candidate target autoantigen for autoimmune-mediated demyelination. We have evaluated the effect of a recombinant form of the PLP protein, Delta PLP4, in a murine model of experimental autoimmune encephalomyelitis (EAE). PLP-specific T-cell r esponses were observed following immunization of SJL/J, PL/J and SWR m ice with Delta PLP4, demonstrating processing of the protein to severa l distinct antigenic epitopes. Clinical EAE associated with inflammati on and demyelination in the CNS also developed after sensitization of mice with Delta PLP4 in adjuvant. Conversely, tolerance to, Delta PLP4 in adult mice and prevention of PLP peptide 139-151-induced EAE was i nduced by intravenous injection of soluble Delta PLP4. The prevention of disease onset was paralleled by a significant reduction in demyelin ation and CNS inflammatory cell infiltration and diminished PLP139-151 -specific T-cell proliferative responses. These results are consistent with the establishment of peripheral T-cell tolerance and reinforce t he notion that recombinant myelin antigens and intravenous tolerance i nduction may prove useful in the modulation of the human demyelinating disease, multiple sclerosis (MS). (C) 1997 Elsevier Science B.V.