Interferonγ plays a critical down-regulatory role in myelin oligodendrocyte glycoprotein induced autoimmune encephalomyelitis

Cytokines and effector T cell subsets causing autoimmune CNS disease

“…Thus, where do we stand at the moment? Il12p35 À/À mice, Il12rb2 À/À mice, Ifng À/À mice, Ifngr À/À mice, Il17 À/À mice, Il21 À/À mice, Il21r À/À mice, Il22 À/À mice, Tnf À/À mice, and Tnfr(p75) À/À mice are not resistant to EAE although all of these cytokines are either required for the development of Th1 responses or are signature effector cytokines of Th1 or Th17 cells [31][32][33]121,133,134,[169][170][171]. On the other hand, Il23p19 À/À mice, Il23r À/À mice, Il6 À/À mice, T cell conditional gp130 À/À mice, and Gmcsf À/À mice are resistant to EAE corroborating the importance of the IL-23/Th17 axis for the development of chronic inflammation and autoimmunity [36,87,142,172,173].…”

“…Consistent with this idea, Tbx21 À/À (T-bet deficient) mice were resistant to MOG induced EAE and neutralizing antibodies to the p40 subunit of IL-12 reduced the disease severity in EAE mice [28,29]. However, as of the mid 1990s it was difficult to reconcile the Th1 concept of EAE with the observation that the newly generated Ifng À/À mice and Ifngr À/À mice as well as Il12p35 À/À mice were not resistant to EAE, but were even hypersusceptible to the disease [30][31][32]. It was later discovered that the p40 subunit of IL-12 not only paired with p35 to form the biologically active heterodimeric molecule of IL-12, but also with a p19 subunit to form a cytokine that was termed IL-23 [33].…”

“…Indeed, in mice, high levels of IFN-c could be detected in the CNS at the peak of EAE disease, but declined during recovery [65]. However, unexpectedly, mice deficient for IFN-c or IFN-c receptor were fully susceptible to EAE and even experienced an EAE with higher morbidity and mortality [30,31]. Although it is now known that IFN-c is also pro-apoptotic and initiates the contraction of effector T cell populations [66,67], development of EAE in the genetic absence of IFN-c eliminated this cytokine as unique non-redundant pathogenic factor in T cell mediated organ-specific autoimmunity.…”

Cytokine expression by inflammatory cells obtained from the spinal cords of Lewis rats with experimental autoimmune encephalomyelitis induced by inoculation with myelin basic protein and adjuvants

“…The persistence of IFNexpression during clinical recovery could be consistent with a down-regulatory role for this cytokine in EAE. Such a down-regulatory role is suggested by the observations that: (1) administration of antibody to IFN-can enhance EAE (Billiau et al, 1988;Voorthuis et al, 1990), (2) intraventricular IFN-can suppress EAE (Voorthuis et al, 1990), (3) abrogation of IFN-expression makes BALB/c mice susceptible to EAE (Krakowski and Owens, 1996), and (4) EAE is more severe in IFN-receptor deficient mice (Willenborg et al, 1996). IFN-might down-regulate EAE through its ability to induce apoptosis of activated T cells (Liu and Janeway, 1990).…”

IFNG polymorphisms are associated with gender differences in susceptibility to multiple sclerosis

“…13 However, it is unclear whether the increased IFNg expression is a deleterious or a disease limiting response in EAE, as IFNg receptor knockout mice are more susceptible to EAE than wild-type mice. 14,15 Transgenic mice overexpressing IFNg in the central nervous system under the control of an oligodendrocyte-specific promoter develop extensive primary demyelination compared to wild-type mice. 16,17 IFNg may exert deleterious effects directly on myelinating cells and also through activation of macrophages and microglia.…”