Animal models of myasthenia gravis

Premkumar Christadoss, Mathilde Poussin, Caishu Deng

Research output: Contribution to journalArticle

132 Citations (Scopus)

Abstract

Myasthenia gravis (MG) is an antibody-mediated, autoimmune neuromuscular disease. Animal models of experimental autoimmune myasthenia gravis (EAMG) can be induced in vertebrates by immunization with Torpedo californica acetylcholine receptors (AChR) in complete Freund's adjuvant. The MHC class II genes influence the cellular and humoral immune response to AChR and are involved in the development of clinical EAMG in mice. A dominant epitope within the AChR α146-162 region activates MHC class II-restricted CD4 cells and is involved in the production of pathogenic anti-AChR antibodies by B cells. Neonatal or adult tolerance to this T-cell epitope could prevent EAMG. During an immune response to AChR in vivo, multiple TCR genes are used. The CD28-B7 and CD40L-CD40 interaction is required during the primary immune response to AChR. However, CTLA-4 blockade augmented T- and B-cell immune response to AChR and disease. Cytokines IFN-γ and IL-12 upregulate, while IFN-α downregulates, EAMG pathogenesis. However, the Th2 cytokine IL-4 fails to play a significant role in the development of antibody-mediated EAMG. Systemic or mucosal tolerance to AChR or its dominant peptide(s) has prevented EAMG in an antigen-specific manner. Antigen-specific tolerance and downregulation of pathogenic cytokines could achieve effective therapy of EAMG and probably MG. (C) Academic Press.

Original languageEnglish (US)
Pages (from-to)75-87
Number of pages13
JournalClinical Immunology
Volume94
Issue number2
DOIs
StatePublished - Feb 2000

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Autoimmune Experimental Myasthenia Gravis
Myasthenia Gravis
Cholinergic Receptors
Animal Models
Cytokines
Antibodies
B-Lymphocytes
Down-Regulation
Antigens
Torpedo
Neuromuscular Diseases
MHC Class II Genes
CD40 Ligand
T-Lymphocyte Epitopes
Freund's Adjuvant
Interleukin-12
Humoral Immunity
Cellular Immunity
Interleukin-4
Autoimmune Diseases

Keywords

  • Autoimmunity
  • Cytokines
  • MHC class II
  • Myasthenia gravis
  • Pathogenesis
  • Specific therapy
  • T-cell epitope

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Pathology and Forensic Medicine

Cite this

Christadoss, P., Poussin, M., & Deng, C. (2000). Animal models of myasthenia gravis. Clinical Immunology, 94(2), 75-87. https://doi.org/10.1006/clim.1999.4807

Animal models of myasthenia gravis. / Christadoss, Premkumar; Poussin, Mathilde; Deng, Caishu.

In: Clinical Immunology, Vol. 94, No. 2, 02.2000, p. 75-87.

Research output: Contribution to journalArticle

Christadoss, P, Poussin, M & Deng, C 2000, 'Animal models of myasthenia gravis', Clinical Immunology, vol. 94, no. 2, pp. 75-87. https://doi.org/10.1006/clim.1999.4807
Christadoss, Premkumar ; Poussin, Mathilde ; Deng, Caishu. / Animal models of myasthenia gravis. In: Clinical Immunology. 2000 ; Vol. 94, No. 2. pp. 75-87.
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