Interferon-γ confers resistance to experimental allergic encephalomyelitis


  • Michelle Krakowski,

    Corresponding author
    1. Department of Microbiology and Immunology, McGill University, Montreal, Canada
    • Neuroimmunology Unit, Room 033, Montreal Neurological Institute, 3801 Rue University, Montreal, Quebec H3A 2B4, Canada, Fax: +1-514-398-7371
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  • Trevor Owens

    1. Department of Microbiology and Immunology, McGill University, Montreal, Canada
    2. Department of Neurology and Neurosurgery, McGill University, Montreal, Canada
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In experimental allergic encephalomyelitis (EAE), T cells infiltrate the central nervous system (CNS) and induce inflammation. These CD4+ T cells secrete interferon (IFN)-γ, levels of which correlate with disease severity, and which is proposed to play a key role in disease induction. Many strains of mice are resistant to EAE. We have studied the effect of deletion of IFN-γ on the ability to induce EAE in resistant BALB/c-backcrossed mice. As expected, only 0–6 % of BALB/c or BALB/c-backcrossed mice developed EAE when immunized with myelin basic protein in adjuvant. Strikingly, abrogation of IFN-γ expression by targeted disruption of the IFN-γ gene (GKO mice) converted them to a susceptible phenotype. As many as 71 % of these IFN-γ-deficient mice developed EAE, a frequency comparable to that seen with the susceptible SJL/J strain. In addition, EAE was of unusually high severity in mice lacking IFN-γ. Immunological characteristics of disease in IFN-γ-deficient mice were comparable to those seen in susceptible (SJL/J) mice with EAE, including perivascular infiltration in the CNS and order-of-magnitude increases for both CD3 γ chain and TNF-α mRNA levels in the spinal cord. We thus demonstrate that lack of IFN-γ converts an otherwise EAE-resistant mouse strain to become susceptible to disease. Therefore, in BALB/c mice, IFN-γ confers resistance to EAE.