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Absence of IL-4 facilitates the development of chronic autoimmune myasthenia gravis in C57BL/6 mice.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2003 Jan 01; Vol. 170 (1), pp. 604-12. - Publication Year :
- 2003
-
Abstract
- Myasthenia gravis (MG) is a T cell-dependent, Ab-mediated autoimmune disease. Ab against muscle acetylcholine receptor (AChR) cause the muscular weakness that characterizes MG and its animal model, experimental MG (EMG). EMG is induced in C57BL6 (B6) mice by three injections of Torpedo AChR (TAChR) in adjuvant. B6 mice develop anti-TAChR Ab that cross-react with mouse muscle AChR, but their CD4+ T cells do not cross-react with mouse AChR sequences. Moreover, murine EMG is not self-maintaining as is human MG, and it has limited duration. Several studies suggest that IL-4 has a protecting function in EMG. Here we show that B6 mice genetically deficient in IL-4 (IL-4-/-) develop long-lasting muscle weakness after a single immunization with TAChR. They develop chronic self-reactive Ab, and their CD4+ T cells respond not only to the TAChR and TAChR subunit peptides, but also to several mouse AChR subunit peptides. These results suggest that in B6 mice, regulatory mechanisms that involve IL-4 contribute to preventing the development of a chronic Ab-mediated autoimmune response to the AChR.
- Subjects :
- Amino Acid Sequence
Animals
Autoantibodies blood
B7-1 Antigen biosynthesis
CD4-Positive T-Lymphocytes immunology
CD4-Positive T-Lymphocytes metabolism
CD40 Antigens biosynthesis
Chronic Disease
Epitopes, T-Lymphocyte immunology
Genetic Predisposition to Disease
Immunization
Injections, Subcutaneous
Interferon-gamma metabolism
Lymphocyte Activation genetics
Mice
Mice, Inbred C57BL
Mice, Knockout
Myasthenia Gravis, Autoimmune, Experimental blood
Peptide Fragments immunology
Receptors, Cholinergic administration & dosage
Receptors, Cholinergic immunology
Severity of Illness Index
Spleen cytology
Spleen immunology
Spleen metabolism
Torpedo immunology
Interleukin-4 deficiency
Interleukin-4 genetics
Myasthenia Gravis, Autoimmune, Experimental genetics
Myasthenia Gravis, Autoimmune, Experimental immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 170
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 12496449
- Full Text :
- https://doi.org/10.4049/jimmunol.170.1.604