INTERFERON-GAMMA CONFERS RESISTANCE TO EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS

In experimental allergic encephalomyelitis (EAE), T cells infiltrate t he 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 r esistant BALB/c-backcrossed mice. As expected, only 0-6 % of BALB/c or BALB/c-backcrossed mice developed EAE when immunized with myelin basi c 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-defici ent mice developed EAE, a frequency comparable to that seen with the s usceptible SJL/J strain. In addition, EAE was of unusually high severi ty in mice lacking IFN-gamma. Immunological characteristics of disease in IFN-gamma-deficient mice were comparable to those seen in suscepti ble (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 r esistance to EAE.