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Animal models of myasthenia gravis.
Animal models of myasthenia gravis.
- Source :
-
Clinical immunology (Orlando, Fla.) [Clin Immunol] 2000 Feb; Vol. 94 (2), pp. 75-87. - Publication Year :
- 2000
-
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 alpha146-162 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-gamma and IL-12 upregulate, while IFN-alpha 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.<br /> (Copyright 2000 Academic Press.)
- Subjects :
- Animals
Autoantibodies blood
CD4 Antigens immunology
Cytokines immunology
Histocompatibility Antigens Class II immunology
Humans
Mice
Receptors, Cholinergic immunology
Disease Models, Animal
Myasthenia Gravis immunology
Myasthenia Gravis pathology
Myasthenia Gravis therapy
Myasthenia Gravis, Autoimmune, Experimental immunology
Myasthenia Gravis, Autoimmune, Experimental pathology
Myasthenia Gravis, Autoimmune, Experimental therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1521-6616
- Volume :
- 94
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Clinical immunology (Orlando, Fla.)
- Publication Type :
- Academic Journal
- Accession number :
- 10637092
- Full Text :
- https://doi.org/10.1006/clim.1999.4807