Suppressed clinical experimental autoimmune myasthenia gravis in bm12 mice is linked to reduced intracellular calcium mobilization and IL-10 and IFN-gamma release by acetylcholine receptor-specific T cells.
Class II MHC mutant bm12 mice have an increased resistance to experimental autoimmune myasthenia gravis (EAMG) compared to C57BL/6 mice. In vitro, this relative resistance was mainly associated with a reduced cytokine response to acetylcholine receptor (AChR) and its dominant pathogenic peptide alpha 146-162, whereas the response to the epitope alpha 111-126 remained intact. Calcium mobilization after stimulation of AChR-immune T cells with AChR or alpha 146-162 peptide, but not alpha 111-126 peptide, was decreased in bm12 compared to C57BL/6. Thus, the reduced incidence of clinical EAMG in bm12 is linked to lower IFN-gamma and IL-10 release, and intracellular calcium mobilization by alpha 146-162-specific T cells.
Poussin
Mathilde A
MA
Department of Microbiology, University of Pennsylvania Medical Center, Philadelphia, PA 19104-6076, USA.
Fuller
Claudette L
CL
Goluszko
Elzbieta
E
Reyes
Victor E
VE
Braciale
Vivian L
VL
Christadoss
Premkumar
P
D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D007108:Immune Tolerance / Q000235:genetics*; D007113:Immunity, Innate / Q000235:genetics* / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D007424:Intracellular Fluid / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation / Q000235:genetics; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology; D011950:Receptors, Cholinergic / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D010446:Peptide Fragments; D011950:Receptors, Cholinergic; D016753:Interleukin-10; D007371:Interferon-gamma; D002118:Calcium