Absence of IFN-γ or IL-12 has different effects on experimental myasthema gravis in C57BL/6 mice

Peter I. Karachunski, Norma S. Ostlie, Cristina Monfardini, Bianca M. Conti-Fine

Research output: Contribution to journalArticlepeer-review

69 Scopus citations


Immunization with acetylcholine receptor (AChR) causes experimental myasthenia gravis (EMG). Th1 cells facilitate EMG development. IFN-γ and IL- 12 induce Th1 responses: we investigated whether these cytokines are necessary for EMG development. We immunized wild-type (WT) C57BL/6 mice and IFN-γ and IL-12 knockout mutants (IFN-γ(-/-), IL-12(-/-)) with Torpedo AChR (TAChR). WT and IFN-γ(-/-) mice developed EMG with similar frequency, IL- 12(-/-) mice were resistant to EMG. All strains synthesized anti-AChR Ab that were not IgM or IgE. WT mice had anti-AChR IgG1, IgG2b, and IgG2c, IFN-γ(-/- ) mice had significantly less IgG2c, and IL-12(-/-) mice less IgG2b and IgG2c. All mice had IgG bound to muscle synapses, but only WT and IFN-γ(-/-) mice had complement; WT mice had both IgG2b and IgG2c, IFN-γ(-/-) only IgG2b, and IL-12(-/-) neither IgG2b nor IgG2c. CD4+ cells from all AChR- immunized mice proliferated in response to AChR and recognized similar epitopes. After stimulation with TAChR, CD4+ cells from IFN-γ(-/-) mice secreted less IL-2 and similar amounts of IL-4 and IL-10 as WT mice. CD4+ cells from IL-12(-/-) mice secreted less IFN-γ, but more IL-4 and IL-10 than WT mice, suggesting that they developed a stronger Th2 response to TAChR. The EMG resistance of IL-12(-/-) mice is likely due to both reduction of anti- TAChR Ab that bind complement and sensitization of modulatory Th2 cells. The reduced Th1 function of IFN-γ(-/-) mice does not suffice to reduce all complement-fixing IgG subclasses, perhaps because as in WT mice a protective Th2 response is missing.

Original languageEnglish (US)
Pages (from-to)5236-5244
Number of pages9
JournalJournal of Immunology
Issue number10
StatePublished - May 15 2000


Dive into the research topics of 'Absence of IFN-γ or IL-12 has different effects on experimental myasthema gravis in C57BL/6 mice'. Together they form a unique fingerprint.

Cite this