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

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

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 C57Bl/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.

Authors

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

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Oral treatment with peptide Tα146-162 protects from clinical EAMG. Evalu...
Oral treatment with peptide Tα146-162 protects from clinical EAMG. Evaluation of mice fatigability in different treatment groups by the inverted hang test. The evaluation performed at the end of the experiments is reported. A group of normal mice was included for comparison in each experiment. The mean holding times (± SEM) for PBS- and Tα146-162–treated mice were 0.6 ± 0.1 minutes and 5.7 ± 1.3, respectively (P = 0.009) (a). The mean holding times for control peptide– and Tα146-162–treated mice were 1.6 ± 0.3 minutes and 8.0 ± 1.2, respectively (P < 0.001) (b).