Oral administration of an immunodominant T-cell epitope downregulates Th1/Th2 cytokines and prevents experimental myasthenia gravis

Fulvio Baggi, Francesca Andreetta, Elisabetta Caspani, Monica Milani, Renato Longhi, Renato Mantegazza, Ferdinando Cornelio, Carlo Antozzi

Research output: Contribution to journalArticle

Abstract

The mucosal administration of the native antigen or peptide fragments corresponding to immunodominant regions is effective in preventing or treating several T cell-dependent models of autoimmune disease. No data are yet available on oral tolerance with immunodominant T-cell peptides in experimental autoimmune myasthenia gravis (EAMG), an animal model of B cell- dependent disease. We report that oral administration of the T-cell epitope α146-162 of the Torpedo californica acetylcholine receptor (TAChR) α- subunit suppressed T-cell responses to AChR and ameliorated the disease in C57B1/6 (B6) mice. Protection from EAMG was associated with reduced serum Ab's to mouse AChR and reduced AChR loss in muscle. The effect of Tα146-162 feeding was specific; treatment with a control peptide did not affect EAMG manifestations. The protective effect induced by peptide Tα146-162 was mediated by reduced production of IFN-γ, IL-2, and IL-10 by TAChR-reactive cells, suggesting T-cell anergy. TGF-β-secreting Th3 cells did not seem to be involved in tolerance induction. We therefore demonstrate that feeding a single immunodominant epitope can prevent an Ab-mediated experimental model of autoimmune disease.

Original languageEnglish
Pages (from-to)1287-1295
Number of pages9
JournalJournal of Clinical Investigation
Volume104
Issue number9
Publication statusPublished - Nov 1999

ASJC Scopus subject areas

  • Medicine(all)

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