Absence of IL-4 facilitates the development of chronic autoimmune myasthenia gravis in C57BL/6 mice.
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.
Ostlie
Norma
N
Department of Biochemistry, University of Minnesota, Minneapolis, MN 55455, USA.
Milani
Monica
M
Wang
Wei
W
Okita
David
D
Conti-Fine
Bianca M
BM
D000595:Amino Acid Sequence; D000818:Animals; D001323:Autoantibodies / Q000097:blood; D018122:B7-1 Antigen / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D019013:CD40 Antigens / Q000096:biosynthesis; D002908:Chronic Disease; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D020022:Genetic Predisposition to Disease; D007114:Immunization; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000172:deficiency* / Q000235:genetics*; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000097:blood / Q000235:genetics* / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D011950:Receptors, Cholinergic / Q000008:administration & dosage / Q000276:immunology; D012720:Severity of Illness Index; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014101:Torpedo / Q000276:immunology
D001323:Autoantibodies; D018122:B7-1 Antigen; D019013:CD40 Antigens; D018984:Epitopes, T-Lymphocyte; D010446:Peptide Fragments; D011950:Receptors, Cholinergic; D015847:Interleukin-4; D007371:Interferon-gamma