Role for interferon-gamma in rat strains with different susceptibility to experimental autoimmune myasthenia gravis.
Experimental autoimmune myasthenia gravis (EAMG) is caused by autoantibodies against the nicotinic acetylcholine receptor (AChR) at the neuromuscular postsynaptic membrane and represents an animal model of myasthenia gravis in human. Recent studies highlighted the roles of TH1 cytokines (IFN-gamma, IL-12), rather than TH2 cytokines (IL-4), in the pathogenesis of EAMG by using homozygous (-/-) knockout mice with an EAMG-susceptible genetic background. To further evaluate a role for IFN-gamma, we injected recombinant rat IFN-gamma (rrIFN-gamma) at the time of immunization with AChR in complete Freund's adjuvant to EAMG-susceptible Lewis rats and EAMG-resistant Wistar Furth (WF) rats. RrIFN-gamma enhanced Lewis rat EAMG. The exacerbated muscular weakness was associated with higher levels of anti-AChR IgG and enhanced TNF-alpha responses. Anti-AChR IgG antibody levels were augmented to a similar extent as in Lewis rats, however, the identical immunization and IFN-gamma injection induced only mild and transient EAMG in WF rats due to the default TH3 phenotype development and inherent low TH1 responses. We conclude that IFN-gamma plays a major role in the pathogenesis of EAMG in the Lewis rat, but fails to break disease resistance in the WF rat.
Wang
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Experimental Neurology Unit, Huddinge University Hospital, Stockholm, S-141 86, Sweden. Hua-Bing.Wang@neurotec.ki.se
Shi
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Li
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van der Meide
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Ljunggren
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D000818:Animals; D000906:Antibodies / Q000276:immunology; D004198:Disease Susceptibility; D005260:Female; D020022:Genetic Predisposition to Disease; D007132:Immunoglobulin Isotypes / Q000097:blood; D007371:Interferon-gamma / Q000502:physiology*; D008213:Lymphocyte Activation / Q000187:drug effects; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000235:genetics* / Q000276:immunology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew / Q000276:immunology*; D011920:Rats, Inbred WF / Q000276:immunology*; D011950:Receptors, Cholinergic / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000235:genetics
D000906:Antibodies; D007132:Immunoglobulin Isotypes; D012333:RNA, Messenger; D011950:Receptors, Cholinergic; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma