Lymphotoxin-alpha deficiency completely protects C57BL/6 mice from developing clinical experimental autoimmune myasthenia gravis.
A complete prevention of clinical experimental autoimmune myasthenia gravis (EAMG) was observed in lymphotoxin (LT)-alpha deficient (LT-alpha(-/-)) mice compared to LT-alpha(+/+) mice when immunized with acetylcholine receptor. However, only a partial prevention of clinical EAMG incidence was observed in LT-beta(-/-) mice compared to LT-beta(+/+) mice. LT-alpha(-/-)and LT-beta(-/-) mice had lower mean titers of total IgG, IgG(1), IgG(2a) and IgG(2b) and higher or equal mean titers of IgM anti-AChR antibodies compared to controls. Therefore, LT-alpha(-/-)and LT-beta(-/-) AChR immunized mice are capable of mounting a primary (IgM) humoral immune response to AChR, but are less capable of switching to the pathogenic anti-AChR IgG isotypes. LT could play a significant role in the pathogenesis of myasthenia gravis.
Goluszko
E
E
Department of Microbiology and Immunology, University of Texas Medical Branch, 301 University Boulevard, 3.142 MRB, Galveston, TX 77555-1070, USA.
Hjelmström
P
P
Deng
C
C
Poussin
M A
MA
Ruddle
N H
NH
Christadoss
P
P
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D001323:Autoantibodies / Q000097:blood; D051940:B7-2 Antigen; D015870:Gene Expression / Q000276:immunology; D016056:Immunodominant Epitopes / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D008233:Lymphotoxin-alpha / Q000235:genetics* / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000276:immunology*; D011950:Receptors, Cholinergic / Q000276:immunology*; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology
D015703:Antigens, CD; D001323:Autoantibodies; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D016056:Immunodominant Epitopes; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008233:Lymphotoxin-alpha; D008562:Membrane Glycoproteins; D011950:Receptors, Cholinergic; D018124:Receptors, Tumor Necrosis Factor