Induction of antigen-specific tolerance for the treatment of ongoing, relapsing autoimmune encephalomyelitis: a comparison between oral and peripheral tolerance

J Immunol. 1997 Jul 15;159(2):1036-44.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Oral
  • Animals
  • Antigens / administration & dosage
  • Antigens / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Epitopes / administration & dosage
  • Epitopes / immunology
  • Female
  • Immune Tolerance*
  • Mice
  • Myelin Proteins / administration & dosage
  • Myelin Proteins / immunology*
  • Myelin Proteolipid Protein*
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / immunology*

Substances

  • Antigens
  • Epitopes
  • Myelin Proteins
  • Myelin Proteolipid Protein
  • Peptide Fragments
  • myelin proteolipid protein (139-151)