Oral administration of an immunodominant T-cell epitope downregulates Th1/Th2 cytokines and prevents experimental myasthenia gravis
Fulvio Baggi, … , Ferdinando Cornelio, Carlo Antozzi
Fulvio Baggi, … , Ferdinando Cornelio, Carlo Antozzi
Published November 1, 1999
Citation Information: J Clin Invest. 1999;104(9):1287-1295. https://doi.org/10.1172/JCI7121.
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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 administration of purified TAChR suppresses antigen-specific T-cell...
Oral administration of purified TAChR suppresses antigen-specific T-cell responses in B6 mice. Mice were given 1 mg × 4 doses of TAChR orally every other day and were immunized with TAChR 2 days after the last feeding. Mice were sacrificed 10 days after immunization for T-cell proliferation studies. Data are represented as SI ± SEM. Open columns: PBS-treated mice (n = 6); filled columns: TAChR-treated mice (n = 5). The effect of TAChR feeding on T-cell proliferation was statistically significant (P < 0.05) at 2.5 and 0.025 μg/mL of TAChR. The average cpm of cultured LN cells in the absence of antigen were 277 ± 59 for PBS-treated and 404 ± 125 for TAChR-treated mice.