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 autoimmune demyelinating disease of the central nervous system that serves as an animal model for multiple sclerosis. Various forms of Ag-specific 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-coupled splenocytes and oral administration of PLP139-151, for efficacy in the reduction of established, chronic clinical EAE. PLP139-151-coupled 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 IFN-gamma production, while concomitantly increasing IL-4 production. Oral administration of PLP139-151 did 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 PLP139-151-specific IL-2 and IFN-gamma production. These results suggest that PLP139-151 peptide-induced tolerance is an efficacious treatment for ongoing, R-EAE when the peptide is coupled to chemically fixed splenocytes and not when given orally.
Kennedy
K J
KJ
Department of Pathology, Northwestern University Medical School, Chicago, IL 60611, USA.
Smith
W S
WS
Miller
S D
SD
Karpus
W J
WJ
D000284:Administration, Oral; D000818:Animals; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D000939:Epitopes / Q000008:administration & dosage / Q000276:immunology; D005260:Female; D007108:Immune Tolerance; D051379:Mice; D009185:Myelin Proteins / Q000008:administration & dosage / Q000276:immunology*; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology*
D000941:Antigens; D000939:Epitopes; D009185:Myelin Proteins; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments; C435023:myelin proteolipid protein (139-151)