Experimental autoimmune myasthenia gravis induced in mice without adjuvant: genetic susceptibility and adoptive transfer of weakness.
The induction of experimental autoimmune myasthenia gravis (EAMG) in mice in the absence of adjuvant was investigated. The essential biochemical features of the disease were induced using a protocol including a primary intrasplenic immunization (1 microgram Torpedo acetylcholine receptor, AChR) followed by booster immunizations with the same dose at 2 and 6 weeks (intraperitoneal) and at 14 weeks (intrasplenic). These features included serum antibodies reactive with mouse AChR, antibody complexed with AChR in vivo, and AChR loss from motor endplates. None of the mice immunized with AChR in adjuvant developed weakness. By contrast, a few mice (less than 5%) immunized without adjuvant became overtly weak and these clinical signs could be adoptively transferred to irradiated recipients, suggesting a possible model for testing immunotherapeutic strategies. Of the nine mouse strains immunized (on six different H-2 haplotypes: a, b, d, k, q, and s) only those with the H-2k haplotype did not develop the biochemical features associated with EAMG. In an F1 cross the genotype (H-2b) was dominant in conferring susceptibility to CBA mice (H-2k).
Jermy
A C
AC
Department of Neurological Sciences, Royal Free Hospital, School of Medicine, London, UK.
Fisher
C A
CA
Vincent
A C
AC
Willcox
N A
NA
Newsom-Davis
J
J
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D001323:Autoantibodies / Q000032:analysis; D001327:Autoimmune Diseases / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D005221:Fatigue; D007114:Immunization / Q000379:methods; D007116:Immunization, Passive; D017710:Lymphocyte Transfusion; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains / Q000276:immunology; D009045:Motor Endplate / Q000276:immunology; D009132:Muscles / Q000276:immunology; D009157:Myasthenia Gravis / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D011950:Receptors, Cholinergic / Q000276:immunology; D014101:Torpedo
D000276:Adjuvants, Immunologic; D001323:Autoantibodies; D011950:Receptors, Cholinergic