Suppression of experimental autoimmune myasthenia gravis by nasal administration of acetylcholine receptor.
Experimental autoimmune myasthenia gravis (EAMG) is a well established animal model, which can be induced in various animal species and strains with acetylcholine receptor (AChR) and represents an experimental counterpart of human myasthenia gravis (MG). Current immunotherapies of both EAMG and MG are non-specific and limited by their toxicity. Tolerance to EAMG has been achieved by oral administration of milligram quantities of Torpedo AChR. In the present report we demonstrate that nasal administration of microgram doses of Torpedo AChR to female Lewis rats prior to immunization with Torpedo AChR and complete Freund's adjuvant resulted in the prevention of subsequently induced EAMG, the suppression of serum anti-AChR antibody levels, the decrease of delayed-type hypersensitivity responses to AChR, as well as the suppression of AChR-specific immunoglobulin G-secreting cells, AChR-reactive interferon-gamma-secreting cells and T cell proliferation in peripheral lymphoid organs, particularly in popliteal and inguinal lymph nodes regional to immunization. We conclude that clinical signs of EAMG can be efficiently prevented by nasal administration of AChR in parallel with the downregulation of both B and T cell responses specific to AChR.
Ma
C G
CG
Division of Neurology, Karolinska Institute, Huddinge University Hospital, Sweden.
Zhang
G X
GX
Xiao
B G
BG
Link
J
J
Olsson
T
T
Link
H
H
D000281:Administration, Intranasal; D000818:Animals; D003208:Concanavalin A; D004557:Electric Organ / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006968:Hypersensitivity, Delayed; D007074:Immunoglobulin G / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D009157:Myasthenia Gravis / Q000276:immunology* / Q000503:physiopathology / Q000517:prevention & control; D004676:Myelin Basic Protein / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D011950:Receptors, Cholinergic / Q000276:immunology* / Q000302:isolation & purification; D013997:Time Factors; D014101:Torpedo
D007074:Immunoglobulin G; D004676:Myelin Basic Protein; D011950:Receptors, Cholinergic; D003208:Concanavalin A; D007371:Interferon-gamma