Interferon-gamma confers resistance to experimental allergic encephalomyelitis

Eur J Immunol. 1996 Jul;26(7):1641-6. doi: 10.1002/eji.1830260735.


In experimental allergic encephalomyelitis (EAE), T cells infiltrate the central nervous system (CNS) and induce inflammation. These CD4+ T cells secrete interferon (IFN)-gamma, 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-gamma 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-gamma expression by targeted disruption of the IFN-gamma gene (GKO mice) converted them to a susceptible phenotype. As many as 71% of these IFN-gamma-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-gamma. Immunological characteristics of disease in IFN-gamma-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 gamma chain and TNF-alpha mRNA levels in the spinal cord. We thus demonstrate that lack of IFN-gamma converts an otherwise EAE-resistant mouse strain to become susceptible to disease. Therefore, in BALB/c mice, IFN-gamma confers resistance to EAE.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Crosses, Genetic
  • Disease Susceptibility / immunology
  • Encephalomyelitis, Autoimmune, Experimental / genetics*
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Genetic Predisposition to Disease
  • Immunity, Innate / genetics
  • Interferon-gamma / genetics
  • Interferon-gamma / physiology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Spinal Cord / immunology
  • Spinal Cord / metabolism
  • Tumor Necrosis Factor-alpha / genetics
  • Up-Regulation / genetics
  • Up-Regulation / immunology


  • Tumor Necrosis Factor-alpha
  • Interferon-gamma