Nasal tolerance to experimental autoimmune myasthenia gravis: tolerance reversal by nasal administration of minute amounts of interferon-gamma.
Tolerance to B cell-mediated experimental autoimmune myasthenia gravis (EAMG), an animal model for myasthenia gravis (MG) in humans, can be achieved by nasal administration of the autoantigen acetylcholine receptor (AChR). Nasal tolerance induction requires only 1/1000 of the amount of AChR used for oral tolerance induction, but is as effective in preventing EAMG. To investigate whether nasally induced tolerance to EAMG can be influenced by nasal administration of cytokines, recombinant rat IFN-gamma (total 5000 U/rat), a combination of AChR and IFN-gamma or AChR alone was given nasally to Lewis rats before immunization with AChR and complete Freund's adjuvant (CFA). One additional group of rats received the same amount of AChR nasally in conjunction with IFN-gamma (total 5000 U/rat) intraperitoneally. AChR given alone nasally induced effective tolerance to EAMG whereas rats receiving AChR + IFN-gamma by the nasal route exhibited a similar disease pattern, and similarly escalated T and B cell responses to AChR when compared to control EAMG rats. In contrast, administration of IFN-gamma i.p. together with AChR nasally did not affect the induction of tolerance to EAMG. IFN-gamma given alone nasally did not affect clinical EAMG. This study demonstrates that nasal tolerance can be modulated by nasal administration of minute amounts of IFN-gamma. Nasal administration of certain cytokines with beneficial effects might broaden the effectiveness of applying nasal tolerance as a potential therapeutic means of preventing autoimmune diseases.
Li
H L
HL
Division of Neurology, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
Shi
F D
FD
Bai
X F
XF
Huang
Y M
YM
van der Meide
P H
PH
Xiao
B G
BG
Link
H
H
D000281:Administration, Intranasal; D000818:Animals; D000915:Antibody Affinity; D001323:Autoantibodies / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004306:Dose-Response Relationship, Immunologic; D007108:Immune Tolerance / Q000187:drug effects*; D018928:Immunity, Mucosal; D007132:Immunoglobulin Isotypes / Q000276:immunology; D007371:Interferon-gamma / Q000008:administration & dosage*; D008213:Lymphocyte Activation; D009157:Myasthenia Gravis / Q000276:immunology* / Q000517:prevention & control; D051381:Rats; D011917:Rats, Inbred Lew; D011978:Receptors, Nicotinic / Q000276:immunology*
D001323:Autoantibodies; D007132:Immunoglobulin Isotypes; D011978:Receptors, Nicotinic; D007371:Interferon-gamma