Interferon-gamma confers resistance to experimental allergic encephalomyelitis.
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.
Krakowski
M
M
Department of Microbiology and Immunology, McGill University, Montreal, Canada. Michelle@rclvax.medcor.mcgill.ca
Owens
T
T
D000818:Animals; D003433:Crosses, Genetic; D004198:Disease Susceptibility / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D020022:Genetic Predisposition to Disease; D007113:Immunity, Innate / Q000235:genetics; D007371:Interferon-gamma / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D013116:Spinal Cord / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma