INDUCTION OF ANTIGEN-SPECIFIC TOLERANCE FOR THE TREATMENT OF ONGOING,RELAPSING AUTOIMMUNE ENCEPHALOMYELITIS - A COMPARISON BETWEEN ORAL AND PERIPHERAL TOLERANCE

Experimental autoimmune encephalomyelitis (EAE) is a T cell-mediated a utoimmune demyelinating disease of the central nervous system that ser ves as an animal model for multiple sclerosis, Various forms of Ag-spe cific tolerance have been used prophylactically to prevent development of acute EAE, Here we compare the induction of Ag-specific tolerance using two regimens, proteolipid protein 139-151 (PLP139-151) peptide-c oupled splenocytes and oral administration of PLP139-151, for efficacy in the reduction of established, chronic clinical EAE, PLP139-151-cou pled splenocytes and not oral administration of PLP139-151 was able to down-regulate established EAE, including subsequent relapses, PLP139- 151 peptide-coupled splenocytes were effective at reducing Ag-specific T cell proliferation and IL-2 and lFN-gamma production, while concomi tantly increasing IL-4 production, Oral administration of PLP139-151 d id not reduce IL-2 or IFN-gamma production and appeared to increase Ag -specific T cell proliferation, Neither multiple high nor low doses of PLP139-151 were effective at decreasing ongoing clinical EAE or PLP13 9-151-specific IL-2 and IFN-gamma production, These results suggest th at PLP139-151 peptide-induced tolerance is an efficacious treatment fo r ongoing, R-EAE when the peptide is coupled to chemically fixed splen ocytes and not when given orally.