Oral administration of an immunodominant T-cell epitope downregulates Th1/Th2 cytokines and prevents experimental myasthenia gravis.
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 alpha146-162 of the Torpedo californica acetylcholine receptor (TAChR) alpha-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 Talpha146-162 feeding was specific; treatment with a control peptide did not affect EAMG manifestations. The protective effect induced by peptide Talpha146-162 was mediated by reduced production of IFN-gamma, IL-2, and IL-10 by TAChR-reactive cells, suggesting T-cell anergy. TGF-beta-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.
Baggi
F
F
Department of Neuromuscular Diseases, National Neurological Institute "C. Besta," 20133 Milan, Italy.
Andreetta
F
F
Caspani
E
E
Milani
M
M
Longhi
R
R
Mantegazza
R
R
Cornelio
F
F
Antozzi
C
C
D000284:Administration, Oral; D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage* / Q000494:pharmacology; D051379:Mice; D009157:Myasthenia Gravis / Q000276:immunology / Q000517:prevention & control*; D010455:Peptides / Q000494:pharmacology; D011950:Receptors, Cholinergic / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology; D014158:Transcription, Genetic / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000235:genetics
D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D010455:Peptides; D011950:Receptors, Cholinergic; D016212:Transforming Growth Factor beta