Nasal tolerance in experimental autoimmune myasthenia gravis (EAMG): induction of protective tolerance in primed animals

Clin Exp Immunol. 1998 Mar;111(3):506-12. doi: 10.1046/j.1365-2249.1998.00521.x.


Nasal administration of microg doses of acetylcholine receptor (AChR) is effective in preventing the development of B cell-mediated EAMG in the Lewis rat, a model for human MG. In order to investigate whether nasal administration of AChR modulates ongoing EAMG, Lewis rats were treated nasally with AChR 2 weeks after immunization with AChR and Freund's complete adjuvant. Ten-fold higher amounts of AChR given nasally (600 microg/rat) were required to ameliorate the manifestations of EAMG compared with the amounts necessary for prevention of EAMG. In lymph node cells from rats receiving 600 microg/rat of AChR, AChR-induced proliferation and interferon-gamma (IFN-gamma) secretion were reduced compared with control EAMG rats receiving PBS only. The anti-AChR antibodies in rats treated nasally with 600 microg/rat of AChR had lower affinity, reduced proportion of IgG2b and reduced capacity to induce AChR degradation. Numbers of AChR-reactive IFN-gamma and tumour necrosis factor-alpha (TNF-alpha) mRNA-expressing lymph node cells from rats treated nasally with 600 microg/rat of AChR were suppressed, while IL-4, IL-10 and transforming growth factor-beta (TGF-beta) mRNA-expressing cells were not affected. Collectively, these data indicate that nasal administration of AChR in ongoing EAMG induced selective suppression of Th1 functions, i.e. IFN-gamma and IgG2b production, but no influence on Th2 cell functions. The impaired Th1 functions may result in the production of less myasthenic anti-AChR antibodies and contribute to the amelioration of EAMG severity in rats treated with AChR 600 microg/rat by the nasal route.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Animals
  • Antibody Specificity
  • Cytokines / biosynthesis
  • Disease Models, Animal
  • Female
  • Freund's Adjuvant / administration & dosage
  • Immune Tolerance*
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Immunoglobulin Isotypes / blood
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Myasthenia Gravis / immunology*
  • Myasthenia Gravis / therapy*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Inbred Lew
  • Receptors, Cholinergic / drug effects
  • Receptors, Cholinergic / immunology*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • Th1 Cells / drug effects
  • Th1 Cells / immunology
  • Th2 Cells / drug effects
  • Th2 Cells / immunology
  • Torpedo


  • Cytokines
  • Immunoglobulin G
  • Immunoglobulin Isotypes
  • RNA, Messenger
  • Receptors, Cholinergic
  • Freund's Adjuvant