Prevention of experimental myasthenia gravis by nasal administration of synthetic acetylcholine receptor T epitope sequences

Peter I. Karachunski, Norma S. Ostlie, David K. Okita, Bianca M. Conti-Fine

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73 Scopus citations

Abstract

T cell tolerization prevents and improves T cell-mediated experimental autoimmune diseases. We investigated here whether similar approaches could be used for antibody (Ab)-mediated autoimmune diseases. Myasthenia gravis, caused by IgG Ab against muscle acetylcholine receptor (AChR), is perhaps the best characterized of them. We used an animal model, experimental myasthenia gravis induced in C57Bl/6 mice by immunization with Torpedo acetylcholine receptor (TAChR), to demonstrate that nasal administration of synthetic sequences of the TAChR α-subunit-forming epitopes recognized by anti-TAChR CD4+ T helper cells (residues α150-169, α181-200, and α360-378), given before and during immunization with TAChR, causes decreased CD4+ responsiveness to those epitopes and to TAChR, reduced synthesis of anti- TAChR Ab, and prevented experimental myasthenia gravis. These effects were not induced by nasal administration of synthetic epitopes of diphtheria toxin. Secretion of IL-2, IL-4, and IL-10 by spleen T cells from TAChR immunized mice, in response to challenge with TAChR in vitro, indicated that in sham-tolerized mice only Th1 cells responded to TAChR, while peptide- treated mice had also an AChR-specific Th2 response. The TAChR peptide treatment induced also in vitro anergy to the TAChR of the spleen T cells, which was reversed by IL-2.

Original languageEnglish (US)
Pages (from-to)3027-3035
Number of pages9
JournalJournal of Clinical Investigation
Volume100
Issue number12
DOIs
StatePublished - Dec 15 1997

Keywords

  • Acetylcholine receptor
  • Autoimmunity
  • Mice
  • Nasal tolerance
  • T cells

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